Analysis of cisapride in neonatal plasma using high-performance liquid chromatography with a base-stable column and fluorescence detection

A simple, selective, sensitive and precise high-performance liquid chromatographic plasma assay for the prokinetic drug cisapride is described. Alkalinised samples of plasma (100 mu l) were extracted with 1.0 ml of 10% (v/v) isopropanol in chloroform, dried, redissolved in mobile phase and injected. Chromatography was performed at 20 degrees C by pumping a mobile phase of acetonitrile (370 ml) in pH 5.2, 0.02 M phosphate buffer (630 mi) at 1.0 ml/min through a C-8 Symmetry column. Cisapride and the internal standard were detected by fluorescence monitoring at 295 nm (excitation) and 350 nm (emission), and were eluted 5 min and 8 min, respectively; after injection. Calibration plots in bovine serum albumin (3% w/v) were linear (r > 0.999) from 5 to 250 ng/ml. Intra-day and inter-day precision (C.V.) was 9.5%, or less, and the accuracy was within 5.5% of the nominal concentration over the range 8-200 ng/ml. Total assay recovery was above 82%. Endogenous plasma components, the major cisapride metabolite (norcisapride), and other drugs used in neonatal pharmacotherapeutics did not interfere

Population pharmacokinetics of enterally administered cisapride in young infants with gastro-oesophageal reflux disease

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 1 h(-1) kg(-1), 21.91, 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