Pharmacokinetics and clinical efficacy of lorazepam in children with severe malaria and convulsions.
OBJECTIVE
To investigate the pharmacokinetics and clinical efficacy of intravenous (i.v.) and intramuscular (i.m.) lorazepam (LZP) in children with severe malaria and convulsions.


METHODS
Twenty-six children with severe malaria and convulsions lasting > or =5 min were studied. Fifteen children were given a single dose (0.1 mg kg(-1)) of i.v. LZP and 11 received a similar i.m. dose. Blood samples were collected over 72 h for determination of plasma LZP concentrations. Plasma LZP concentration-time data were fitted using compartmental models.


RESULTS
Median [95% confidence interval (CI)] LZP concentrations of 65.1 ng ml(-1) (50.2, 107.0) and 41.4 ng ml(-1) (22.0, 103.0) were attained within median (95% CI) times of 30 min (10, 40) and 25 min (20, 60) following i.v. and i.m. administration, respectively. Concentrations were maintained above the reported therapeutic concentration (30 ng ml(-1)) for at least 8 h after dosing via either route. The relative bioavailability of i.m. LZP was 89%. A single dose of LZP was effective for rapid termination of convulsions in all children and prevention of seizure recurrence for >72 h in 11 of 15 children (73%, i.v.) and 10 of 11 children (91%, i.m), without any clinically apparent respiratory depression or hypotension. Three children (12%) died.


CONCLUSIONS
Administration of LZP (0.1 mg kg(-1)) resulted in rapid achievement of plasma LZP concentrations within the reported effective therapeutic range without significant cardiorespiratory effects. I.m administration of LZP may be more practical in rural healthcare facilities in Africa, where venous access may not be feasible.
Muchohi
Simon N
SN
Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre for Geographic Medicine Research (Coast), Kilifi, Kenya. sndirangu@kilifi.kemri-wellcome.org
Obiero
Kenneth
K
Newton
Charles R J C
CR
Ogutu
Bernhards R
BR
Edwards
Geoffrey
G
Kokwaro
Gilbert O
GO
D000349:Africa; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008140:Lorazepam / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D012423:Rural Health; D012640:Seizures / Q000188:drug therapy*; D013223:Statistics as Topic
D000927:Anticonvulsants; D008140:Lorazepam