Pharmacokinetics and clinical efficacy of lorazepam in children with severe malaria and convulsions

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Lorazepam (LZP) may be a more useful anticonvulsant to stop convulsions in children with severe malaria (SM) than diazepam, since it has a longer duration of action and can be given by other routes, such as intramuscular (i.m. WHAT THIS STUDY ADDS• Administration of LZP (i.v. or i.m.) at the currently recommended dose (0.1 mg kg -1 ) resulted in rapid achievement of plasma LZP concentrations within the reported effective therapeutic range without clinically significant cardiorespiratory effects.• A single dose of LZP was effective in the rapid termination of convulsions in all children, and prevention of seizure recurrence for >72 h in 11 of 15 (73%) children and 10 of 11 (91%) children after i.v. and i.m. administration, respectively. AIMTo investigate the pharmacokinetics and clinical efficacy of intravenous (i.v.) and intramuscular (i.m.) lorazepam (LZP) in children with severe malaria and convulsions. METHODSTwenty-six children with severe malaria and convulsions lasting Ն5 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. ) 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. RESULTS Median

Population Pharmacokinetics and Exploratory Pharmacodynamics of Lorazepam in Pediatric Status Epilepticus

“…Another study in children (median age 32 months [range 8–91]) with severe malaria and convulsions reported complete cessation of seizures with an i.v. lorazepam dose of 0.1 mg/kg, but 4/15 [27%] later had seizures recur [22]. …”

Pharmacological sedation management in the paediatric intensive care unit

“…Data on a PK‐PD relationship of lorazepam for sedation are lacking. Pharmacokinetics are well‐described in children with seizures and status epilepticus and a PBPK model underscores the low elimination rate in neonates and the higher elimination rate in children around 2 years of age . Still, a clear evidence‐based dosing regimen for critically ill children is not yet available (see Table for ongoing paediatric lorazepam studies).…”

Epilepsies et crises épileptiques aiguës chez l’enfant en Afrique subsaharienne: défis et espoirs

“…Chez les enfants présentant la malaria sévère, une dose (0,1 mg/kg) du LZP administré par intraveineuse (IV) ou intramusculaire (IM) avait stoppé toutes les convulsions endéans 16 et 27 minutes respectivement. Septante-deux heures après, la même dose était capable de prévenir la récidive dans 73% et 91% des cas après l'administration du LZP en IV et en IM respectivement [ 58 ]. Administré par voie intranasale, le LZP (100µg/kg) avait stoppé 73% des convulsions endéans 10 minutes contre 61,3% après l'administration de paraldéhyde (0,2ml/kg) en IM dans l’étude de Ahmad et al [ 59 ].…”