1. PHA-794428 is a PEGylated version of somatropin (human growth hormone). The pharmacokinetics of PHA-794428 have been studied in humans following single subcutaneous administration (dose range 10-500 g kg-1). In the same study the pharmacokinetics of somatropin were also determined following a 3.6 mg (51 g kg-1) subcutaneous dose. Comparison of the pharmacokinetics of both molecules indicates that PEGylation of somatropin with a 40 kD PEG results in a ten- to 20-fold increase in area under the curve and a similar increase in half-life when compared with somatropin in human (at equivalent subcutaneous doses). 2. Literature data indicate that somotropin is cleared by two mechanisms. The first processes is clearance by glomerular filtration. This is a passive, non-capacity-limited process. A second, capacity-limited, process is mediated by interaction with growth hormone receptors present in a number of tissues including the liver. It is hypothesized that PHA-794428 shares the same clearance mechanisms. However, the addition of the PEG moiety has modulated the clearance by both of these processes. Pharmacokinetic modelling of human serum concentration data obtained for these molecules strongly supports this hypothesis. The renal clearance is reduced due to the increased size of the molecule (Cl/F reduced from 9.6 to 0.1 l h(-1) for somatropin and PHA-794428, respectively). In addition, the reduction in growth hormone receptor affinity has reduced the clearance mediated by interaction with this receptor (somatropin Km = 3.6 g l(-1) and Vmax = 104 g h-1/PHA-794428 Km = 53 g l(-1) and Vmax = 84 g h(-1)).

To evaluate the effects of pantothenic acid during wound healing processes, fibroblastic cell cultures originating from foreskin were established and subcultured by trypsinization. PA (40 µg/ml) was added to the basal culture medium. The cell proliferation was estimated by cell count and determination of3H-thymidine incorporation. The protein synthesis and secretion were determined by dosage in the cells and in the culture medium.