Pharmacokinetics and Tolerability of Buspirone during Oral Administration to Children and Adolescents with Anxiety Disorder and Normal Healthy Adults

• Published in: Journal of clinical pharmacology 2001-12, Vol.41 (12), p.1351-1358
• Main Authors: Salazar, Daniel E., Frackiewicz, Edyta J., Dockens, Randy, Kollia, Georgia, Fulmor, I. Edgar, Tigel, Phillip D., Uderman, Howard D., Shiovitz, Thomas M., Sramek, John J., Cutler, Neal R.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anti-Anxiety Agents - administration & dosage; Anti-Anxiety Agents - adverse effects; Anti-Anxiety Agents - pharmacokinetics; Anxiety Disorders - drug therapy; Anxiety Disorders - metabolism; Area Under Curve; Biological and medical sciences; Buspirone - administration & dosage; Buspirone - adverse effects; Buspirone - pharmacokinetics; Child; Electrocardiography - drug effects; Female; Half-Life; Humans; Male; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/00912700122012823

A 21‐day, open‐label, multisite, dose escalation study comprising three demographic groups (children, adolescents, and adults) was performed to determine the pharmacokinetics and tolerability of orally administered buspirone. Thirteen children and 12 adolescents with anxiety disorder and 14 normal healthy adults were escalated from 5 to 30 mg buspirone bid over the 3‐week study. Pharmacokinetic analysis revealed that buspirone was rapidly absorbed in all study groups, reaching peak levels at about 1 hour after administration. Peak plasma buspirone concentrations (Cmax) were highest in children and lowest in adults at all three dose levels (7.5, 15, 30 mg bid). However, 1‐pyrimidinylpiperazine (1‐PP), the primary metabolite of buspirone, exhibited a different plasma concentration‐time profile; Cmax was significantly higher in children than in either adolescents or adults at all concentrations. In addition, TAUC0‐T for 1‐PP was significantly higher in the children cohort relative to adolescents and adults. Buspirone was generally safe and well tolerated at doses up to 30mgbid in adolescents and adults and most of the children. The most frequently reported adverse events in children and adolescents were lightheadedness (68%), headache (48%), and dyspepsia (20%); 2 children withdrew from the study at the higher doses (15 mg and 30 mg bid) due to adverse effects. In adults, the most common adverse effect was somnolence (21.4%); lightheadedness, nausea, vomiting, and diarrhea were also reported, although these were mild in intensity.