Oral bioavailability of clonidine in children.

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.

Steal-induction after clonidine premedication: a comparison of the oral and nasal route.

BACKGROUND: Clonidine premedication in children reliably provides preoperative sedation and anxiolysis, but onset of oral clonidine is known to be slow. Nasal clonidine has been shown to reach peak plasma levels within 10 min in rodents. The aim of the present study was to compare clinical effects and percentage of steal-induction after clonidine premedication by the oral and nasal route. METHODS: Forty children, aged 1-6 years, scheduled for minor infraumbilical surgery, were randomly assigned to receive either pure clonidine 4 microgxkg(-1) intranasally (group CN, n = 20) or clonidine 4 microgxkg(-1) orally in syrup (group CO, n = 20) prior to mask induction. Drug acceptance, preoperative sedation and anxiolysis, quality of mask acceptance, recovery profile and parents' satisfaction were evaluated. RESULTS: Drug acceptance was similar between groups, but quality of taste was significantly better in the oral group. There was no significant difference of preoperative anxiolysis and sedation. The onset of sedative effect was after 38.3 min for oral clonidine and 47.5 min for nasal clonidine. A steal-induction could be performed in 60% of children in each group. Emergence from anesthesia and parents' satisfaction were comparable. CONCLUSIONS: Intranasal clonidine administration has no advantage over the oral route. Clinical effects were similar with both routes; there was a trend towards a faster onset of sedation with oral clonidine. Clonidine premedication causes light sleep, which allows a steal-induction in 60% of patients.