Oral bioavailability of clonidine in children.
Summary of "Oral bioavailability of clonidine in children."
Summary 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.
Affiliation
Department of Physiology & Pharmacology, Section of Anaesthesiology & Intensive Care, Karolinska Institutet, Stockholm, Sweden.
Journal Details
This article was published in the following journal.
Name: Paediatric anaesthesia
ISSN: 1460-9592
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20735802
- DOI: http://dx.doi.org/10.1111/j.1460-9592.2010.03397.x
Medical and Biotech [MESH] Definitions
Indinavir
A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.
Clonidine
An alpha-2 adrenergic agonist that crosses the blood-brain barrier. Clonidine acts centrally by reducing sympathetic tone, resulting in a fall in diastolic and systolic blood pressure and a reduction in heart rate. It also acts peripherally, and this peripheral activity may be responsible for the transient increase in blood pressure seen during rapid intravenous administration. (From Martindale, the Extra Pharmacopoeia, 30th ed, p350)
Oral Medicine
A branch of dentistry dealing with diseases of the oral and paraoral structures and the oral management of systemic diseases. (Hall, What is Oral Medicine, Anyway? Clinical Update: National Naval Dental Center, March 1991, p7-8)
Poliovirus Vaccine, Oral
A live vaccine containing attenuated poliovirus, types I, II, and III, grown in monkey kidney cell tissue culture, used for routine immunization of children against polio. This vaccine induces long-lasting intestinal and humoral immunity. Killed vaccine induces only humoral immunity. Oral poliovirus vaccine should not be administered to immunocompromised individuals or their household contacts. (Dorland, 28th ed)
Oral Hygiene
The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health.
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