Key result
Elderly subjects had a 70% higher mean systemic exposure to valsartan compared to young volunteers, though this difference is not considered clinically relevant.
Why the study?
Does age affect the pharmacokinetics of a single oral dose of 80 mg valsartan in healthy volunteers?
Does age affect the pharmacokinetics of a single oral dose of 80 mg valsartan in healthy volunteers?
Effect estimate: 70% increase in AUC(0-infinity)
While systemic exposure to valsartan is higher in some elderly subjects, the difference is not considered clinically relevant and does not warrant initial dose adjustment based on age alone.
Supports no age-based dose adjustment in healthy elderly; leaves open PK variability in frail or comorbid patients.
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 male and six female subjects. Mean systemic exposure to valsartan was higher in the elderly when compared with the young (AUC(0-24 h), 52% increase 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 between 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 volunteers. This higher systemic exposure in five of the elderly subjects is not thought to be of clinical relevance when data from the patient population are considered. Other covariates--such as body weight, comedication, creatinine clearance, valsartan kinetics (absorption rate, distribution, and elimination)--did not explain the higher AUC in this subset of the elderly group. Data from the present study were compared with population kinetic data obtained from larger clinical trials including hypertensive patients in all age groups. Using this population approach, there was no difference in the pharmacokinetics of valsartan between male and female patients. Also, a relationship between plasma clearance of valsartan and age was established. The median age of patients in the hypertensive pool was 55 years. For an average 70-year-old patient, plasma clearance of valsartan is predicted to fall by 22% compared 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 treatment was well tolerated.
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Sioufi et al. (1998) studied Healthy volunteers (n=24). Valsartan vs. Young volunteers was evaluated on Systemic exposure to valsartan (AUC) (70% increase in AUC(0-infinity)). Elderly subjects had a 70% higher mean systemic exposure to valsartan compared to young volunteers, though this difference is not considered clinically relevant.
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