THE EFFECT OF AGE ON THE PHARMACOKINETICS OF VALSARTAN

Twelve young (mean age 23 years, range 18-28) and 12 elderly (mean age 76 years, range 65-89) volunteers were given a single oral dose of 80 mg valsartan after an overnight fast. Each group consisted of six mal e and six female subjects. Mean systemic exposure to valsartan was hig her in the elderly when compared with the young (AUC(0-24 h), 52% incr ease and AUC(0-infinity), 70% increase). Variability, as shown by the coefficient of variation (CV), was larger for the elderly subjects and ANOVA of the log transformed AUC showed a significant difference betw een the two groups. This difference was largely brought about by five elderly subjects (one male, four females), whose AUC was about 2-fold higher than the rest of the group. For the remaining elderly subjects, plasma valsartan AUC was similar to that observed for the young volun teers. This higher systemic exposure in five of the elderly subjects i s not thought to be of clinical relevance when data from the patient p opulation are considered. Other covariates-such as body weight, comedi cation, creatinine clearance, valsartan kinetics (absorption rate, dis tribution, and elimination)-did not explain the higher AUC in this sub set of the elderly group. Data from the present study were compared wi th population kinetic data obtained from larger clinical trials includ ing hypertensive patients in all age groups. Using this population app roach, there was no difference in the pharmacokinetics of valsartan be tween male and female patients. Also, a relationship between plasma cl earance of valsartan and age was established. The median age of patien ts in the hypertensive pool was 55 years. For an average 70-year-old p atient, plasma clearance of valsartan is predicted to fall by 22% comp ared with an average 55-year-old. For the population, this difference is not sufficient to warrant initial dose adjustment based on age per se. The covariate age, does not completely explain the variability in the pharmacokinetics of valsartan within the general population. The t reatment was well tolerated. (C) 1998 John Wiley & Sons, Ltd.