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Population Pharmacokinetics of Amlodipine in Hypertensive Children and Adolescents
Author(s) -
Flynn Joseph T.,
Nahata Milap C.,
Mahan John D.,
Portman Ronald J.
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006289844
Subject(s) - amlodipine , nonmem , pharmacokinetics , medicine , population , volume of distribution , dosing , pharmacology , blood pressure , environmental health
A population pharmacokinetic study was conducted in 74 hypertensive children (mean age 10.4 ± 4.4 years [mean ± SD]) receiving amlodipine (mean dose 0.17 ± 0.13 mg/kg/d) chronically. Multiple blood samples were obtained from each subject to characterize amlodipine pharmacokinetics. Plasma amlodipine concentrations were determined by liquid chromatography/mass spectrophotometry with multiple‐reaction monitoring detection. Population pharmacokinetic analysis was performed using NONMEM. Amlodipine concentrations were similar in subjects dosed either once or twice daily. Amlodipine pharmacokinetics were well described by a 1‐compartment model with first‐order absorption and elimination. For a subject at the population median weight (45 kg), predicted apparent clearances (CL/F) were 23.7 L/h for males and 17.6 L/h for females, and the apparent volume of distribution (V/F) was 25.1 L/kg. Dosing frequency did not appear to affect amlodipine concentrations in children. Weight‐adjusted CL/F and V/F of amlodipine in younger children were significantly greater than in older children, suggesting a need for higher doses when treating young children with amlodipine.