RESUMO
BACKGROUND: Oral clonidine is used as premedication in children. The bioavailability of clonidine given orally in adults is 75-100% but is unknown in children. METHODS: Children (3-10 years) undergoing adenotonsillectomy were administered oral clonidine 4 mcg·kg(-1) mixed with apple fruit drink as premedication. Intravenous plasma was assayed for clonidine concentration at 5, 15, 30, 45 min and 1, 2, 4, 6, 12, 18 h after administration. Clonidine plasma concentrations were determined by liquid chromatography-mass spectroscopy, and pharmacokinetic parameters were calculated using nonlinear effects mixed-effects models. Current data were pooled with published time-concentration profiles from children (n = 49) administered intravenous clonidine to determine oral bioavailability. RESULTS: There were eight children studied (age 3-10 years, weight 10.5-36 kg). A two-compartment model with first-order absorption and elimination was used to describe time-concentration profiles. Population parameter estimates (CV%; 95% CI), standardized to a 70-kg person, were absorption half-life (Tabs), 0.45 (85.1; 0.221-0.884) h, absorption lag time (Tlag), 0.148 (91.2; 0.002-0.316) h, Clearance (CL) 17.9 (30.3; 16-20.3) l·h(-1) per 70 kg, between compartment clearance (Q) 121 (44.3; 80.1-165) l·h(-1) per 70 kg, central volume (V1) 81.2 (71.5; 60.7-105) l·70 kg(-1), peripheral volume of distribution (V2) 113 (33.9; 91-131) l·70 kg(-1). The oral bioavailability was 55.4% (CV 6.4%; 95% CI 0.469, 0.654). CONCLUSIONS: Clonidine administered with an apple fruit drink displays a variable and relatively slow absorption after oral administration (T(max) 1.04 h, C(max) 0.77 mcg·l(-1)). The oral bioavailability was 55.4%, which is less than reported in adults. Consequently, higher oral doses of clonidine (per kg) are required when this formulation is used to achieve concentrations similar to those reported in adults.