PHARMACOKINETICS AND PHARMACODYNAMICS OF FAMOTIDINE IN CHILDREN

The pharmacokinetics and pharmacodynamics of intravenous famotidine we re studied in 12 children (1.1-12.9 years of age; mean weight +/- stan dard deviation = 27.6 +/- 21.2 kg) who were given the drug for prophyl actic management of stress ulceration. After a 0.5-mg/kg infusion of f amotidine, timed blood (n = 10) and urine (n = 6) samples and repeated evaluations of intragastric pH (n = 13) were obtained from each subje ct. Pharmacokinetic parameters were determined from curve fitting of s erum concentration data. The mean (+/- SD) maximum serum concentration (C-max) was 527.6 +/- 281.2 ng/mL, the elimination half-life (t1/2) w as 3.2 +/- 3.0 hours, and the apparent steady-state volume of distribu tion (Vd(ss)) was 2.4 +/- 1.7 L/kg. Plasma clearance (Cl) and renal cl earance (Cl-R) were 0.70 +/- 0.34 L/hr/kg and 0.43 +/- 0.24 L/hr/kg, r espectively. Over 24 hours, 73.0 +/- 27.3% of the dose was excreted un changed in the urine (F-el). Pharmacodynamic analysis of gastric pH da ta using the sigmoid E(max) model predicted that 50% of the maximal ef fect of famotidine (EC(50)) occurs at a serum concentration of 26.0 +/ - 13.2 ng/mL. Children who did not have an initial intragastric pH les s than or equal to 4 did not have a significant response in pH after r eceiving famotidine. Although Vd(ss) and CI were higher in these child ren than those seen in adults, statistically significant relationships between these parameters and age were not observed in the study popul ation. The pharmacodynamics and pharmacokinetics of famotidine in chil dren older than one year of age appear to be similar to those noted in adults.