Single- and multiple-dose pharmacokinetics of pioglitazone in adolescents with type 2 diabetes.
This study assessed the single- and multiple-dose pharmacokinetics of 3 doses (15 mg, 30 mg, and 45 mg) of pioglitazone in 36 adolescents with type 2 diabetes. Blood samples were obtained over a 48-hour interval after the first dose (day 1) and over a 72-hour interval after the last dose (day 15) of pioglitazone and were assayed for pioglitazone and active metabolites (M-III and M-IV). Pioglitazone systemic exposure increased dose dependently but was less than dose proportional during multiple dosing. The median peak pioglitazone concentration occurred at 2 hours. The mean half-life was 8 to 9 hours for pioglitazone and 24 to 32 hours for M-III and M-IV, with similar values at each dose level. During multiple dosing, accumulation for pioglitazone was negligible, but it reached 2.5- to 3.0-fold for M-III and M-IV. The sustained total serum concentration of active compounds during multiple dosing provides the basis for once-daily dose administration of pioglitazone in adolescents.
Christensen
Michael L
ML
University of Tennessee, 50 North Dunlap, Room 306, Memphis, TN 38103, USA.
Meibohm
Bernd
B
Capparelli
Edmund V
EV
Velasquez-Mieyer
Pedro
P
Burghen
George A
GA
Tamborlane
William V
WV
D000293:Adolescent; D019540:Area Under Curve; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D009325:Nausea / Q000139:chemically induced; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone