Abstract:
AIMS:To investigate the pharmacokinetics of enterally administered cisapride suspension in young infants being treated for gastro-oesophageal reflux disease. METHODS:Plasma cisapride concentrations in 49 subjects (weight: 825-5010 g; n=108 samples, median two per patient; concentration: 14.8-170 ng ml-1 ) were fitted to a one-compartment model with first-order absorption and elimination in the NONMEM program using a logarithmic transformation of the observed and predicted concentrations. Fitting was achieved using the first order conditional estimation (FOCE) method with interaction between the interpatient and intrapatient variabilities. The interpatient variance of clearance (CL/F ) and volume of distribution (V /F ) and their covariance were estimated using an exponential error model. Intrapatient (residual) variance was estimated using an additive model. RESULTS:The clearance of cisapride was shown to be linearly related to current body weight, slope: 0.538. The typical population values of CL/F, V /F and Ka (absorption rate constant) were 0.538 l h-1 kg-1, 21.9 l, and 2.58 h-1, respectively. The population coefficients of variation (CV%) for CL/F and V/F were 34.4% and 84.3%, respectively. The squared coefficient of correlation between random effects for CL/F and V /F was 0.45. The intrapatient variance was 0.15. V /F and Ka were not influenced significantly by any patient characteristic. CONCLUSIONS:Cisapride pharmacokinetics in infants with reflux disease were satisfactorily described by a one-compartment model. Current weight should be taken into account when calculating maintenance cisapride doses in these infants.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Preechagoon Y,Charles B,Piotrovskij V,Donovan T,Van Peer Adoi
10.1046/j.1365-2125.1999.00068.xkeywords:
subject
Has Abstractpub_date
1999-11-01 00:00:00pages
688-93issue
5eissn
0306-5251issn
1365-2125pii
bcp068journal_volume
48pub_type
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journal_title:British journal of clinical pharmacology
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journal_title:British journal of clinical pharmacology
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