BACKGROUND:Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use. METHODS AND FINDINGS:Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention. HCQ was evaluated in Europe and Africa, and chloroquine (CQ) was evaluated in Asia, (both base equivalent of 155 mg once daily). The primary endpoint was symptomatic COVID-19, confirmed by PCR or seroconversion during the 3-month follow-up period. The secondary and tertiary endpoints were: asymptomatic laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection; severity of COVID-19 symptoms; all-cause PCR-confirmed symptomatic acute respiratory illness (including SARS-CoV-2 infection); participant reported number of workdays lost; genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity (not reported here); and health economic analyses of HCQ and CQ prophylaxis on costs and quality of life measures (not reported here). The primary and safety analyses were conducted in the intention-to-treat (ITT) population. Recruitment of 40,000 (20,000 HCQ arm, 20,000 CQ arm) participants was planned but was not possible because of protracted delays resulting from controversies over efficacy and adverse events with HCQ use, vaccine rollout in some countries, and other factors. Between 29 April 2020 and 10 March 2022, 4,652 participants (46% females) were enrolled (HCQ/CQ n = 2,320; placebo n = 2,332). The median (IQR) age was 29 (23 to 39) years. SARS-CoV-2 infections (symptomatic and asymptomatic) occurred in 1,071 (23%) participants. For the primary endpoint the incidence of symptomatic COVID-19 was 240/2,320 in the HCQ/CQ versus 284/2,332 in the placebo arms (risk ratio (RR) 0.85 [95% confidence interval, 0.72 to 1.00; p = 0.05]). For the secondary and tertiary outcomes asymptomatic SARS-CoV-2 infections occurred in 11.5% of HCQ/CQ recipients and 12.0% of placebo recipients: RR: 0.96 (95% CI, 0.82 to 1.12; p = 0.6). There were no differences in the severity of symptoms between the groups and no severe illnesses. HCQ/CQ chemoprevention was associated with fewer PCR-confirmed all-cause respiratory infections (predominantly SARS-CoV-2): RR 0.61 (95% CI, 0.42 to 0.88; p = 0.009) and fewer days lost to work because of illness: 104 days per 1,000 participants over 90 days (95% CI, 12 to 199 days; p < 0.001). The prespecified meta-analysis of all published pre-exposure RCTs indicates that HCQ/CQ prophylaxis provided a moderate protective benefit against symptomatic COVID-19: RR 0.80 (95% CI, 0.71 to 0.91). Both drugs were well tolerated with no drug-related serious adverse events (SAEs). Study limitations include the smaller than planned study size, the relatively low number of PCR-confirmed infections, and the lower comparative accuracy of serology endpoints (in particular, the adapted dried blood spot method) compared to the PCR endpoint. The COPCOV trial was registered with ClinicalTrials.gov; number NCT04303507. INTERPRETATION:In this large placebo-controlled, double-blind randomised trial, HCQ and CQ were safe and well tolerated in COVID-19 chemoprevention, and there was evidence of moderate protective benefit in a meta-analysis including this trial and similar RCTs. TRIAL REGISTRATION:ClinicalTrials.gov NCT04303507; ISRCTN Registry ISRCTN10207947.

Background: NMU of prescription drugs among adolescents and young adults is increasing problem worldwide.Very few studies have been conducted in this sub-group in Benin.This study aimed to investigate the prevalence and pattern of NMU of psychotropic drugs (anxiolytics, hypnotics, antipsychotics, antidepressants, and mood regulators), factors associated with their use among secondary school students in Parakou and identify abuse cases and dependence.Methods: This cross-sectional study was conducted among students in grades 8-12th aged 10-24 years old.Data were collected using the Alcohol, Smoking and Substance involvement Screening Test (ASSIST), followed by urine drug test using NarcoCheck quick.Participants were selected using a three-stage cluster sampling method.A logistic regression model was used to identify factors associated with NUM of prescription drugs.Results: 13.58% of the students reported lifetime nonmedical use of any prescription drugs, while 8.64% reported past three months' use.The pattern of use revealed that Diazepam was the most widely abused psychotropic drugs (9.47%).Only 0.8% reported using prescription drugs, as shown by urine screening.An association was found between nonmedical use of psychotropic drugs and grade level (p=0.03),lifetime tobacco use (p=0.016),alcohol (p=0.013),cannabis use (0.003), and stimulants use (p=0.026).Among nonmedical users, 21.21% had a hazardous level of use, and 03.03% had dependence.Conclusion: This study showed a high prevalence of NMU of prescription drugs among secondary school students in Parakou.There is a need for prevention and intervention programs to minimize the nonmedical use of prescription drugs in students.

Abstract Background There is a high prevalence of psychoactive substance use among patients with mental health disorders. The optimal treatment of patients with mental health disorders requires an awareness of their history pertaining substance use. Several methods are used to assess the use of substance. Each of them embodies its limitations. This study aimed at assessing the diagnostic capability of a self-report psychoactive substance use among patients at the National Psychiatric University Hospital of Cotonou, Benin. Methods A cross-sectional survey was conducted from August 1, 2021 to November 24, 2021. A total of 157 consenting patients admitted to psychiatric consultations were successively enrolled in the ongoing study. They were screened for the use of psychoactive substance with Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), followed by urine test using the NarcoCheck® kit for qualitative detection of substances or its metabolites. To assess the diagnostic capability, the participants’ self-responses were compared with their urine test results. The sensitivity, specificity, positive and negative predictive values, and kappa coefficient were also calculated. Results The frequency of lifetime psychoactive substance use according to self-report was 81.5% (95% CI: 0.746–0.873), while over the past three months (recent use) was 52.2% (95% CI: 0.441–0.603) and 58.6% based on the urine test. Alcohol, tobacco and cannabis were the most prevalent psychoactive substance used. The overall concordance between self-reported psychoactive substance use and the urine test (gold standard) was moderate (sensitivity = 66%; kappa = 0.46). Self-report cocaine use compared with urine test showed the highest concordance (sensitivity = 100%; kappa = 79%), followed by tobacco (sensitivity = 58%, kappa = 41%). On an average 70% of urine test results were consistent with self-report (VPP). Participants’ were more accurate when they were reporting no psychoactive substance use as suggested by the high negative predictive value (NPV). Conclusion Diagnostic capability of self-reporting of psychoactive substance use among patients admitted to psychiatric consultations was moderate. Therefore self-reporting may not estimate the exact prevalence of psychoactive substance use. Optimal identification of psychoactive substances use in psychiatric patients requires both history and urine testing. The integration of these two approaches is an excellent method to find out the level, frequency and nature of drug used.

The use of psychoactive substances is constantly increasing, particularly among young people. This study aimed to estimate the prevalence, associated factors and the level of dependence of those substances among secondary school students in Benin. This cross‐sectional study included 627 students in grades 8–12, selected using a multi‐stage sampling technique. Data were collected using the ASSIST questionnaire, followed by urine screening. Logistic regression analysis was performed to estimate factors associated with substance use. Overall, the lifetime prevalence of psychoactive substance use was 95.4% (95% CI = 93.4–96.9), while the current use was 78.8% (95% CI = 75.3–81.9). The most commonly used substances in the past 3 months were alcohol, followed by stimulants and tobacco; 221 samples were analysed. Twenty‐two (9.95%) were positive by urine screening. Substances detected were tramadol, fentanyl, THC, K2, BZDs, alcohol, methamphetamine and cotinine. Of the current users, 2.27% (n = 11) were at high risk of dependency. An association was found between substance use and age (p = 0.02). In conclusion, this study came up with a high prevalence of substance use among students. There is a need to develop and implement a health education programme in secondary schools to raise awareness of the potential risks.

Background: Nonmedical use of tramadol among the young Beninese population is an increasing public health concern. However, there is little research on tramadol use in West Africa. Objectives: This study aimed to assess the prevalence, factors associated with nonmedical use of tramadol and to determine the level of therapeutic intervention needed. Methods: A cross-sectional study design and multi-stage sampling method was used among 384 secondary school students, within the age group of 10-24 years old who gave their consent/assent. An interviewer-administered modified questionnaire based on ASSIST was administered. Urinary toxicological test was performed using NarcoCheck (R) quick for qualitative detection of tramadol or its metabolites. Logistic regression analysis was performed to identify factors associated with nonmedical use of tramadol. Results: The average age of our respondents was 17 +/- 2 SD years old; 58.3% were males and 41.7% females. The lifetime prevalence of nonmedical use of tramadol was 9.6% (95% CI: 6.7-12.6) (13.4% males and 4.4% females) and the average age at onset was 14.8 +/- 1.8 years old. Only 1.4% (n = 4) were using tramadol as shown by urine screen. Among users, 45.9% reported a hazardous level of use and required a brief intervention. In a multivariate logistic regression model, tobacco (P < .001), cannabis (p = .023) and amphetamine (p = .037) were significantly associated with nonmedical use of tramadol. The most prevalent motives for nonmedical use of tramadol was experimentation (45.9%) and the leading source for obtaining tramadol was street-level markets (86.5%). Conclusion: These results indicate that nonmedical use of tramadol affects young in Benin and represent a considerable concern among secondary school students.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have garnered considerable attention for their potential to treat or prevent the novel coronavirus disease 2019 (COVID-19) due to in vitro data and preliminary results from certain clinical studies in China and France. These molecules have a long history of use including prophylaxis. Confronted with serious complications leading to intensive care admissions and deaths, these medicines have been recommended and implemented in some risk populations. Our aim was to present the rationale for use of these medicines in chemoprophylaxis pre-exposure or post-exposure and list the clinical trials in progress to evaluate the efficacy for using these two drugs in prevention. Out of the 1324 trials registered on clinical trial.gov, 44 were devoted to CQ or HCQ in chemoprophylaxis. Most pre-exposure setting refer to the recommended dose for treatment of rheumatoid arthritis while very few refer to the recommended dose for malaria prophylaxis.

BACKGROUND & AIMS The objective is to ascertain the pattern of potential drug-drug interactions (pDDIs) and record any observed DDIs and adverse events (AEs) in hospitalized Beninese cardiology patients from Sub-Saharan Africa and analyze all risk factors associated with DDIs and AEs. METHODS It was a prospective study in which data including AEs were assessed from medical files and interview of patients and their relatives. Patients who were treated with more than two drugs and who remained in the hospital for at least 48 hours were included. A computerized database system Pharma IAM- VIDAL version 2011 was used to identify the pattern for potential DDIs. RESULTS 156 patients were included in this study. The prevalence of potential DDIs was estimated at 93 % (145/156).Forty (5.1%) among 804 potential DDIs identified were observed clinically.The observed DDIs were attributable to low blood pressure (27.5%), hyponatremia (22.5%), hemorrhage (20.0%), hyperkalemia (17.5%) and nephrotoxicity (7.5%).The combination of spironolactone and furosemide resulted in hyponatremia while the combination of enoxaparin and potassium resulted in hyperkalemia. ACE inhibitor (or ARAII) in combination with furosemide resulted in the nephrotoxicity cases observed. Enoxaparin, Acetyl salicylic acid, Acenocoumarol and Clopidogrel were decreasingly involved in the pairs of drugs responsible for observed hemorrhages.29 patients out of 156 (18.6%) had at least one AE. AEs were mainly (34.2%) of metabolic type. Severe AEs which represented 18.4% was mostly from nephrotoxicity and metabolic disorders. More than 14 active substances multiplied the risk factor for AEs occurrence by 42, whilemore than 14 days hospitalization increased this risk by 42. CONCLUSION This study highlights the need to optimize treatments by strictly regulating blood pressure, serum sodium and potassium levels, coagulation parameters and looking for clinical signs of hemorrhage. Physician should be aware of certain drug associations that may carry a risk of severe adverse events.

This study aims to evaluate the phytochemistry and antimicrobial activities of the leaves and flowers of Senna italica Mill. Qualitative phytochemical screening was done with method based on differential coloration and precipitation. Thin Layer Chromatography was used for characterization of sennosides in aqueous and hydro-ethanolic extract of leaves and flowers of S. italica. Then HPLC was used for quantification of sennosides. The antifungal activity of the extracts was evaluated on Candida albicans and Trichophyton rubrum by incorporation method. Well diffusion technique, coupled with the microdilution determination of Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (CMB) was used for antibacterial testing. The results of study showed the presence of large groups of secondary metabolites in the leaves and flowers of S. italica including tannins, galic tannins, flavonoids, steroids and some glycosides. TLC test showed that leaves and flowers of S. italica contain sennosides A, B, C and D. HPLC test showed that the content of the sennosides of flowers is higher than that of the dried leaves in the sun. According to daily dose of sennosides recommended, 20 mg to 30 mg as laxative, this dose can be attained with 0.718 to 0.862g of leaf powder or 1.390 to 1.668g of S. italica flower powder. The extracts have no antifungal activity but the hydroethanolic extracts of both leaves and flowers of S. italica have bactericidal activity on strains of S. aureus ATCC 25923, E. coli ATCC 25922 and E. coli clinical strain. This quantification of sennosides is a standardization of the herbal tea of S. italica and will limit these possible side effects. This plant is a good candidate for the development of improved traditional medicine.

L'iatrogénie médicamenteuse est un phénomène préoccupant qui demande que des solutions idoines soient trouvées. L'objectif de cette étude était d'expérimenter une solution pour l'optimisation de la pharmacothérapie en milieu hospitalier : l'intégration du pharmacien dans l'équipe soignante. Il s'agissait d'une étude prospective au cours de laquelle un interne en pharmacie sous la supervision d'un pharmacologue clinicien, a intégré un service de médecine interne. Cent onze prescriptions sur 483 ont conduit à la formulation de 132 interventions pharmaceutiques (IP). Les problèmes liés aux thérapeutiques (PLT) majoritairement détectés étaient une voie et/ou administration inappropriée (47,3 %), une interaction médicamenteuse (16,7 %), une indication non traitée (8,9 %), une prescription non indiquée (6,5 %) et un surdosage potentiel (5,9 %). Les IP qui en résultent sont répartis comme suit : optimisation des modalités d'administration (33,3 %), correction du libellé de prescription (19,7 %), suivi thérapeutique (10,6 %), adaptation posologique (9,1 %), ajout de prescription (9,8 %) et un arrêt de traitement dans 9,1 % des cas. L'intégration du pharmacien dans l'équipe soignante apparaît comme une solution idéale pour l'optimisation de la pharmacothérapie. Drug-related iatrogenesis is a worrying issue requiring adequate solutions. The aim of this study was to test a solution for the optimization of drug therapy in the hospital setting: i.e., including a pharmacist in the healthcare team. A prospective study introduced a resident pharmacist, under the supervision of a clinical pharmacologist, into a department of internal medicine. One hundred and eleven prescriptions out of 483 led to proposals for 132 pharmaceutic interventions. The main therapy-related problems detected were: inappropriate drug administration and/or route (47.3%), drug interaction (16.7%), untreated indications (8.9%), prescription not shown (6.5%) and potential overdose (5.9%). The resulting pharmaceutic interventions comprised: optimization of administration modalities (33.3%), addition of missing items in prescription (19.7%), therapeutic monitoring (10.6%), dose adjustment (9.1%), additional prescription (9.8%) and treatment discontinuation (9.1%). Including a pharmacist in the healthcare team appears to be an ideal solution for optimizing pharmacotherapy.

BACKGROUND:The national strategy against malaria in an endemic country should involve all the health stakeholders. In Benin, the private sector is rarely present in the activities of the National Malaria Control Programme (NMCP), and its surveillance system does not cover private sector outlets that are a non-negligible part of the healthcare system.OBJECTIVE:The aim of this study was to describe the drug delivery practices within private pharmacies of Cotonou and Porto-Novo and the awareness of medicine providers concerning the national policy of malaria treatment.METHODS:A survey was performed among pharmacy staff members responsible for dispensing medicines and providing advice to patients within pharmacies of Cotonou and Porto-Novo. Dispensing/pharmacy assistants ('dispensators') from 82 pharmacies in Cotonou and 19 in Porto-Novo were surveyed. Data entry was performed using Epidata 3.1 software and data analysis was carried out using SPSS software version 21.1. Chi square test was used to compare proportions. A significance threshold of 0.05 was defined for the p value.RESULTS:46% of providers did not know the artemisinin-based combination therapy recommended by the NMCP for treating uncomplicated malaria. 58.7% were not able to recognize the gravity signs of malaria. 89.8% of dispensators were used to deliver an anti-malarial upon patient request, without prior biological confirmation as requested by the NMCP policy.CONCLUSIONS:Dispensing practices within the studied pharmacies from Cotonou and Porto-Novo were not in adequacy with the NMCP guidelines for uncomplicated malaria, which is a striking weakness in the training of drug providers on key elements of the guidelines for managing malaria. The NMCP needs to help dispensator from private pharmacies sector to standardize drug delivery practices according to its guidelines.

Background:To date, no investigation has been carried out to systematically assess pharmacovigilance systems including quality control and resistance monitoring of artemisinin based combination therapies (ACTs) and other essential medicines in Benin.Objective: To assess Benin's pharmacovigilance system, identify the gaps and define elements of strategy which could lead to successful establishment of a functional system in Benin.Methods: Quantitative approach using structure questionnaires was applied to investigate physicians, pharmacists and pharmaceutical industry representatives' knowledge, attitude and practice regarding Adverse Drug Reactions (ADRs) reporting and the pharmacovigilance system in Benin.Specific questions examining the ADRs related to ACTs were also asked.Questions regarding reasons for non-reporting and important factors in a decision to report were also addressed.The Indicator-based Pharmacovigilance Assessment Tool (IPAT) developed by the USAID-funded Strengthening Pharmaceutical Systems (SPS) program was also used to assess the current landscape with different stakeholders.Collecting data on the IPAT indicators was performed during different interviews of key informants.Reviewing documents from different stakeholders was done as well.Results: All physicians and pharmacists have suspected at least one occurrence of ADR in their practice.30.77% physicians and 31.11%pharmacists acknowledged that they faced at least one time ADRs suspected to be associated with antimalarial drug treatment (P-value<0.01).However none of the physicians or the pharmacists have ever reported ADRs to the national pharmacovigilance service.Significant difference (Chi2, P<0.05) was found between the proportion of physicians and pharmacists trained in pharmacovigilance (20% versus 1%).The main reasons for not reporting were ''yellow card not available'' and "not aware about the existence of pharmacovigilance center".A small percentage (6.97%) of representatives of the pharmaceutical companies in the country monitors the safety of their products and none of them have ever reported ADRs to the health authority (DPM).In return, none of the laboratories have ever received a report related to quality or ADRs related to their drugs on the market from LNCQ or DMP.Use of the IPAT tool led to these respective overall scores for core and supplementary indicators: 10 and 7 demonstrating that there is no functional pharmacovigilance system in place.Using these findings, a SWOT analysis was done.The major shortcoming is the lack of expertise in pharmacovigilance despite the availability of qualified human resource in the country.Several recommendations were also made with respect to critical immediate next steps to be taken to ensure that pharmacovigilance and medicine safety systems are developed and sustained in Benin. Conclusions:This study has helped identify some of the critical challenges and barriers to promoting pharmacovigilance including control of quality and monitoring of ACTs resistance in Benin.There is a need to identify and implement adequate human resources use in order to build capacity and sustain the drug safety system for essential medicines and ACTs in particular.The Ministry of Health should involve all relevant stakeholders including the Faculty of Medicine and researchers to discuss these strategies and develop interventions for the successful implementation of pharmacovigilance in Benin.

This study aims to evaluate the in vivo antiviral, immunologic, clinical effects and safety of a supposedly anti-HIV phytotherapy, code-named R019 used for the treatment of HIV/AIDS. This is an open observational study, which involved 32 HIV-1 infected patients, who were followed over a 3-month period. The efficacy evaluation was based on CD4 count, determination of viral load and clinical status. The safety evaluation was based on renal and liver function tests, fasting lipid and glycaemia levels as well as the frequency of other adverse events. The CD4 values increased significantly (mean±SD, 99.03±22.87 cells/µL; P<0.001), as well as Weight and Karnofsky score (2.94±0.67 kg, p<0.001; 4.9, p=0.005 respectively). The viral load decreased significantly (0.91±0.12 log viral load, P<0.0001). R019 did not impair renal or liver functions. Improvement of creatinine clearance was observed (p=0.02). Hemoglobin levels increased (0.38±0.16 gr/dL) whereas cholesterol and glucose levels decreased under R019 treatment (p=0.031, p=0.018 respectively). Main adverse effects were recorded: polyuria (40.5%), drowsiness (21.4%), orexis (19.1%). Immunological, anti-viral and clinical status improved under R019 treatment and a good safety profile was observed for this compound. Further studies would be required to optimize its efficacy and to define its appropriateness for the treatment of HIV disease.

This study aimed at investigating the contribution of CYP2C9 and VKORC1 genetic polymorphisms to inter-individual variability of acenocoumarol pharmacokinetics and pharmacodynamics in Black Africans from Benin. Fifty-one healthy volunteers were genotyped for VKORC1 1173C>T polymorphism. All of the subjects had previously been genotyped for CYP2C9*5, CYP2C9*6, CYP2C9*8, CYP2C9*9 and CYP2C9*11 alleles. Thirty-six subjects were phenotyped with a single 8 mg oral dose of acenocoumarol by measuring plasma concentrations of (R)- and (S)-acenocoumarol 8 and 24 h after the administration using chiral liquid-chromatography tandem mass-spectrometry. International normalized ratio (INR) values were determined prior to and 24 h after the drug intake. The allele frequency of VKORC1 variant (1173C>T) was 1.96% (95% CI 0.0–4.65%). The INR values did not show statistically significant difference between the CYP2C9 genotypes, but were correlated with body mass index and age at 24 h post-dosing (P < 0.05). At 8 h post dose, the (S)-acenocoumarol concentrations in the CYP2C9*5/*8 and CYP2C9*9/*11 genotypes were about 1.9 and 5.1 fold higher compared with the CYP2C9*1/*1 genotype and 2.2- and 6.0-fold higher compared with the CYP2C9*1/*9 group, respectively. The results indicated that pharmacodynamic response to acenocoumarol is highly variable between the subjects. This variability seems to be associated with CYP2C9*5/*8 and *9/*11 variant and demographic factors (age and weight) in Beninese subjects. Significant association between plasma (S)-acenocoumarol concentration and CYP2C9 genotypes suggested the use of (S)-acenocoumarol for the phenotyping purpose. Larger number of subjects is needed to study the effect of VKORC1 1173C>T variant due to its low frequency in Beninese population.

Les differences interindividuelles observees dans la reponse aux medicaments sont en partie dues aux polymorphismes du gene ABCB1 codant pour la glycoproteine-P (P-gp), une proteine de transport des medicaments. Cette revue a pour but de faire le point des connaissances sur les polymorphismes du gene ABCB1 , leur relevance fonctionnelle et clinique et de preciser les particularites au sein de la population noire subsharienne. Le role du gene (ABCB1)MDR1 dans la variabilite pharmacocinetique ou pharmacodynamique a ete demontree clairement in vitro , dans des modeles animaux et lors d’etudes cliniques. Le polymorphisme C3435T est associe a une diminution de l’expression proteique de la P-gp et, par voie de consequence, de son activite. L’existence d’une forte association entre les polymorphismes C3435T et G2677T a suggere alors que la difference fonctionnelle observee peut etre attribuee egalement au deuxieme polymorphisme i.e le G2677T (exon 21). Il a ete identifie chez les noirs africains de nouveaux polymorphismes et des haplotypes particuliers. Differnts travaux ont demontre egalement que le gene ABCB1 intervient dans le suivi therapeutique des patients mis sous immunosuppresseurs, anticancereux, antidepresseurs, antiretroviraux ou antihypertenseurs. Des perspectives fort interessantes en pharmacotherapie avec entre autres l’utilisation de modulateurs de la P-gp sont d’actualite. Mots cles : Pharmacogenetique, glycoproteine-P, medicaments, substances exogenes, Noirs Subsahariens

Aim of the study: To investigate the extent and type of medicinal plants used in self-care by the inhabitants of the Agonlin community in the Republic of Benin. Materials and Methods: A semi-structured questionnaire was used to interview a total of one thousand mothers Results: The prevalence rate of the use of herbal medicines in self-care was found to be 51.04%. One hundred and fourteen (114) plant species belonging to 69 families were reported, each with their local names, medicinal use, and parts used. Of all the indications of the identified plants, fever, headache, abdominal pain, and vomiting were the most frequently reported, with malaria treatment recording the highest usage of plant remedies (22%). The plant part most frequently used was the leaves. Conclusions: This study showed that self-care using medicinal plants is a major part of health care in the Agonlin area. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

The genetically polymorphic cytochrome P450 2C9 (CYP2C9) metabolizes many important drugs. Among them, phenytoin has been used as a probe to determine CYP2C9 phenotype by measuring the urinary excretion of its major metabolite, S-enantiomer of 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). Phenytoin pharmacokinetic is also dependent on the activity of CYP2C19 and p-glycoprotein (ABCB1). To determine the influence of CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms on phenytoin metabolism in a Black population, 109 healthy Beninese subjects received a single 300 mg oral dose of phenytoin. Blood was drawn 4 h after drug intake and urine was collected during the first 8 h. Plasma phenytoin and urine S- and R-enantiomers of p-HPPH were determined by high-performance liquid chromatography. Urinary excretion of (S)-p-HPPH [defined as urinary volume×(S)-p-HPPH urinary concentration] and PMR (defined as the ratio of p-HPPH in urine to 4 h phenytoin plasma concentration), both markers of CYP2C9 activity, were used to determine the functional relevance of new variants of CYP2C9 (*5, *6, *8, *9 and *11) in this population. Plasma phenytoin concentration was significantly associated with ABCB1 haplotype/genotype (P=0.05, Kruskal–Wallis test) and levels increased significantly in the genotype order: wild-type, T3421A and Block-2 genotypes (P=0.015, Jonckheere–Terpstra test). Urinary excretion of (S)-p-HPPH and PMR were significantly associated with the CYP2C9 genotype (P=0.001, analysis of variance (ANOVA) and P<0.0001, Kruskal–Wallis test, respectively) and decreased in the order: CYP2C9*1/*1, CYP2C9*1/*9, CYP2C9*9/*9, CYP2C9*1/*8, CYP2C9*8/*9, CYP2C9*9/*11, CYP2C9*1/*5, CYP2C9*6/*9, CYP2C9*1/*6, CYP2C9*8/*11, CYP2C9*5/*8 and CYP2C9*5/*6 (P<0.001, Jonckheere–Terpstra test). A combined analysis of CYP2C9, 2C19 and ABCB1 revealed that only ABCB1 predicted phenytoin concentration at 4 h and explained 8% of the variability (r2=0.08, P=0.04). On the other hand, only CYP2C9 was predictive for the urinary excretion of (S)-p-HPPH and PMR (r2=0.21, P=0.001 and r2=0.25, P<0.001, respectively). Furthermore, significant relation was found between urinary excretion of (R)-p-HPPH and CYP2C9 genotype (P=0.035) and levels significantly increased in the genotype order: CYP2C9*1/*9, CYP2C9*1/*1, CYP2C9*9/*11, CYP2C9*1/*8 and CYP2C9*1/*5 (P<0.001, Jonckheere–Terpstra test). In summary, the present study demonstrates that, in a Black population, CYP2C9*5, *6, *8 and *11 variants, but not CYP2C9*9, are associated with a decreased phenytoin metabolism. The data also confirm the limited contribution of MDR1 gene to inter-individual phenytoin pharmacokinetic variation.

Background and Aim: Previous data indicate that the urinary losartan/E-3174 ratio is a marker for cytochrome P450 (CYP) 2C9 activity in vivo. The functional impact of CYP2C9(star)5, (star)6, (star)8, and (star)11 polymorphisms in vivo has not been investigated previously in humans.Methods: A single oral dose of losartan (25 mg) was given to 19 Beninese subjects with CYP2C9(star)1/(star)1 (n = 9), (star)1/(star)5 (n = 1), (star)1/(star)6 (n = 1), (star)1/(star)8 (n = 2), (star)1/(star)11 (n = 3), (star)5/(star)6 (n = 1), (star)5/(star)8 (n = 1), and (star)8/(star)11 (n = 1) genotypes. Concentrations of losartan and its active metabolite E-3174 were determined in urine from 0 to 8 hours by HPLC. The losartan/E-3174 metabolic ratio was used as a measure of losartan oxidation in vivo.Results: The urinary losartan/E-3174 ratio in the various genotypes was as follows: 1.85 +/- 2.4 (mean +/- SD) for CYP2C9(star)1/(star)1, 14.6 for CYP2C9(star)1/star5, 4.2 for CYP2C9(star)1/(star)6, 188 for CYP2C9(star)5/(star)6, 11.6 for CYP2C9(star)5/(star)8, 0.44 +/- 0.13 (mean +/- SD) for CYP2C9(star)1/(star)8, 2.2 for CYP2C9(star)8/(star)11, and 5.72 +/- 4.5 (mean +/- SD) for CYP2C9(star)1/(star)11. Compared with the CYP2C9(star)1/(star)1 genotypes, the losartan/E-3174 ratio was significantly different in the CYP2C9(star)5 allele carriers (CYP2C9(star)1/(star)5, CYP2C9(star)5/(star)8, and CYP2C9(star)5/(star)6 genotypes) (P = .01, Mann-Whitney) but was not different in CYP2C9(star)1/(star)8 (P = .16) and CYP2C9(star)1/(star)11 (P = .11) carriers. The urinary losartan/E-3174 ratio of the single CYP2C9(star)1/(star)6 subject was higher than the 95% confidence interval of the mean of the CYP2C9(star)1/(star)1 group (0.0-3.7), whereas the metabolic ratio of the CYP2C9(star)8/(star)11 carrier was inside the 95% confidence interval of the means of the CYP2C9(star)1/(star)1 and CYP2C9(star)1/(star)11 groups (0.0-18).Conclusions: The CYP2C9(star)5 and (star)6 alleles are associated with decreased enzyme activity in vivo compared with the wild-type variant, whereas the CYP2C9(star)8 and (star)11 variants did not appear to have large in vivo effects.