Pharmacokinetics and clinical effect of phenobarbital in children with severe falciparum malaria and convulsions. Journal Article

Authors: Kokwaro, Gilbert O.; Ogutu, Bernhards R.; Muchohi, Simon N.; Otieno, Godfrey O.; Newton, Charles R. J. C.
Article Title: Pharmacokinetics and clinical effect of phenobarbital in children with severe falciparum malaria and convulsions.
Journal Title: British Journal of Clinical Pharmacology
Volume: 56
Issue: 4
ISSN: 03065251
Publisher: Wiley-Blackwell  
Date Published: 2003-10
Start Page: 453
Notes: --- - Article - ! 'Aims Phenobarbital is commonly used to treat status epilepticus in resource-poor countries. Although a dose of 20 mg kg[sup -1] is recommended, this dose, administered intramuscularly (i.m.) for prophylaxis, is associated with an increase in mortality in children with cerebral malaria. We evaluated a 15-mg kg[sup -1] intravenous (i.v.) dose of phenobarbital to determine its pharmacokinetics and clinical effects in children with severe falciparum malaria and status epilepticus. Methods Twelve children (M/F: 11/1), aged 7-62 months, received a loading dose of phenobarbital (15 mg kg[sup -1]) as an i.v. infusion over 20 min and maintenance dose of 5 mg kg[sup -1] at 24 and 48 h later. The duration of convulsions and their recurrence were recorded. Vital signs were monitored. Plasma and cerebrospinal fluid (CSF) phenobarbital concentrations were measured with an Abbott TDx FLx® fluorescence polarisation immunoassay analyser (Abbott Laboratories, Diagnostic Division, Abbott Park, IL, USA). Simulations were performed to predict the optimum dosage regimen that would maintain plasma phenobarbital concentrations between 15 and 20 mg l[sup -1] for 72 h. Results All the children achieved plasma concentrations above 15 mg l[sup -1] by the end of the infusion. Mean (95% confidence interval or median and range for C[sub max]) pharmacokinetic parameters were: area under curve [AUC (0, ?)]: 4259 (3169, 5448) mg l[sup -1].h, t½]: 82.9 (62, 103) h, CL: 5.8 (4.4, 7.3) ml kg[sup -1] h[sup -1], V[sub ss]: 0.8 (0.7, 0.9) 1 kg[sup -1], CSF: plasma phenobarbital concentration ratio: 0.7 (0.5, 0.8; n = 6) and C[sub max]: 19.9 (17.9-27.9) mg l[sup -1]. Eight of the children had their convulsions controlled and none of them had recurrence of convulsions. Simulations suggested that a loading dose of 15 mg kg[sup -1] followed by two maintenance doses of 2.5 mg kg[sup -1] at 24 h and 48 h would maintain plasma phenobarbital concentrations between 16.4 and 20 mg l[sup -1] for 72 h. Conclusions Phenobarbital, given as an i.v. loading dose, 15 mg kg[sup -1], achieves maximum plasma concentrations of greater than 15 mg l[sup -1] with good clinical effect and no significant adverse events in children with severe falciparum malaria. A maintenance dose of 2.5 mg kg[sup -1] at 24 h and 48 h was predicted to be sufficient to maintain concentrations of 15-20 mg l[sup -1] for 72 h, and may be a suitable regimen for treatment of convulsions in these children. [ABSTRACT FROM AUTHOR]' - Copyright of British Journal of Clinical Pharmacology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) - ! 'Accession Number: 11259072; Kokwaro, Gilbert O. 1,2,3; Email Address: Ogutu, Bernhards R. 1,2,3 Muchohi, Simon N. 1,2 Otieno, Godfrey O. 1 Newton, Charles R.J.C. 1,4; Affiliation: 1: Kenya Medical Research Institute (KEMRI) Centre for Geographic Medicine Research (Coast)/Wellcome Trust Collaborative Research Programme 2: Wellcome Trust Research Laboratories, Nairobi 3: Department of Pharmaceutics and Pharmacy Practice, Faculty of Pharmacy, University of Nairobi, Kenya 4: Neurosciences Unit, Institute of Child Health, University of London, UK; Source Info: Oct2003, Vol. 56 Issue 4, p453; Subject Term: ANTICONVULSANTS; Subject Term: MALARIA; Subject Term: CONVULSIONS; Subject Term: PHARMACOKINETICS; Subject Term: TREATMENT; NAICS/Industry Codes: 325411 Medicinal and Botanical Manufacturing; NAICS/Industry Codes: 325410 Pharmaceutical and medicine manufacturing; Number of Pages: 5p; Illustrations: 1 Chart, 1 Graph; Document Type: Article'
SU Authors
  1. Prof. Gilbert Kokwaro
    26 Kokwaro