Chapter 29. Drug Metabolism

Publisher Summary This chapter illustrates drug metabolism that is rapidly proliferating because of the factors that include: rapid advances in methodology, demands of drug regulatory agencies, and unraveling of the mechanisms involved. The use of immunoassays as an analytical method for drugs was in use previously. Researches focused on the clinical pharmacokinetic aspects of diuretics, antiarrhythmic agents, drug use in childbirth and in the postoperative period, and on extracorporeal hemoperfusion techniques. The pharmacokinetics of benzodiazepines has been intensively studied with regard to the effects of subjects age and sex. The elderly had a mean eleven hour prolongation of the half-life of nitrazepam, a mean prolongation of forty-eight hours for diazepam, and no prolongation with lorazepam. Several novel methods for determining the pharmacokinetic parameters have been reported. By using only the area under the plasma concentration versus time curve, the maximum plasma concentration and the time to the maximum concentration, it is possible to determine the equivalence of the apparent first-order rate constants for the absorption and elimination in a one-compartment body model. The metabolism of timolol was compared in animals and man. The oxidative opening of the morpholine ring and the oxidation of the oxypropanolamine side chain appear to be mutually exclusive pathways, the former being of greater importance in rodents and man and the latter in dog. In contrast, 4-ethoxy-2-methyl-5-morpholino-3-(2H)-pyridazinone was metabolized mainly by opening the morpholine ring in mice, rats, rabbits, dogs, and monkeys.