Background and aims The purpose of this study was to develop a population pharmacokinetics model (Pop PK) for ranitidine in newborns, and to determine the effect of nutritional state (NS) and gestational age (GA). The protocol was approved by the bioethics committee.
Methods Fifty newborn (20 females and 30 males) were included. Their (GA) was as follows: 6 pre-term, small (SGA); 20 pre-term, appropriate (AGA); 4 pre-term, large (LGA); 7 SGA of full term; and 13 AGA of full term. Children received 3 mg/kg/day IV bolus of ranitidine; two blood samples were collected at each of the following times obtained randomly to: 0, 0.5, 0.75, 1, 2, 4, and 8 h from every newborn. The ranitidine levels were determined using HPLC technique. For the population pharmacokinetics (Pop PK) of ranitidine was used with MONOLIX MLXTRANS 4.2.2® program; data were fitted to bicompartimental model with first-order kinetics.
Results The population values without effect of covariates were obtained clearance (CL) = 0.267 mL/min (CV = 0.685); volume of distribution (Vd1) = 0.860 L (CV = 0.0642); Vd2 = 0.260 L (CV = 0.47; intercompartmental clearance (Q) = 1.35 (0.279 mL/min. The covariables that influences clearance of ranitidine are gestational age (term infants from 37 to 42 weeks) with decreased CL = 0.241 mL/min, p = 0.008. The BW increase the Vd1 = 1.03 L and reduces the value of Q = 0.556 mL/min (CV = 0.049).
Conclusions Pharmacokinetics of ranitidine depend on (GA) and (NS) of the newborns. This should be considered to determine an adequate dosage treatment, based on respective Pop PK characteristics.
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