AIMS: To evaluate retrospectively the population pharmacokinetics of cetirizine, a second-generation antihistamine, in children. METHODS: Data were pooled from six clinical trials, in which cetirizine was administered orally in various formulations and in single and multiple dosage regimens. The population consisted of 112 children (33 female and 79 male) aged 6 months to 12 years. A one-compartment open model with first-order absorption and elimination was fitted to the plasma concentration-time profiles using nonlinear mixed effects modelling with first-order estimation. RESULTS: A linear association was found between apparent clearance (CL/F) and age with the former increasing by 0.12 l h(-1) per year. The intercept of the relationship was slightly lower for female children (0.59 vs. 0.77 l h(-1) in male). The population estimate of CL/F for an average age of 7 years was 1.61 and 1.43 l h(-1) for male and female children, respectively. A linear association was found between apparent volume of distribution (V/F) and age with the former increasing by 1.4 l year(-1), with an intercept of 4.0 l. The population estimate of V/F for an average age of 7 years was 13.9 l. The magnitudes of interpatient variability were 35.6% for CL/F and 19.7% for V/F. The magnitude of residual variability in cetirizine concentrations was 26.9%. CONCLUSIONS: Population analysis predicts a linear increase in cetirizine CL/F and V/F with age, with CL/F being slightly lower in female children, relative to males of the same age. However, this gender difference probably has no clinical consequences. Since V/F increased more rapidly with age than CL/F, a nonlinear increase in half-life was seen, from < 4 h in infants to near the adult value at 12 years of age. The current recommended dosing regimens that younger children should receive lower but more frequent doses, are confirmed by the present analysis.
AIMS: To evaluate retrospectively the population pharmacokinetics of cetirizine, a second-generation antihistamine, in children. METHODS: Data were pooled from six clinical trials, in which cetirizine was administered orally in various formulations and in single and multiple dosage regimens. The population consisted of 112 children (33 female and 79 male) aged 6 months to 12 years. A one-compartment open model with first-order absorption and elimination was fitted to the plasma concentration-time profiles using nonlinear mixed effects modelling with first-order estimation. RESULTS: A linear association was found between apparent clearance (CL/F) and age with the former increasing by 0.12 l h(-1) per year. The intercept of the relationship was slightly lower for female children (0.59 vs. 0.77 l h(-1) in male). The population estimate of CL/F for an average age of 7 years was 1.61 and 1.43 l h(-1) for male and female children, respectively. A linear association was found between apparent volume of distribution (V/F) and age with the former increasing by 1.4 l year(-1), with an intercept of 4.0 l. The population estimate of V/F for an average age of 7 years was 13.9 l. The magnitudes of interpatient variability were 35.6% for CL/F and 19.7% for V/F. The magnitude of residual variability in cetirizine concentrations was 26.9%. CONCLUSIONS: Population analysis predicts a linear increase in cetirizine CL/F and V/F with age, with CL/F being slightly lower in female children, relative to males of the same age. However, this gender difference probably has no clinical consequences. Since V/F increased more rapidly with age than CL/F, a nonlinear increase in half-life was seen, from < 4 h in infants to near the adult value at 12 years of age. The current recommended dosing regimens that younger children should receive lower but more frequent doses, are confirmed by the present analysis.
Authors: V Spicák; I Dab; R Hulhoven; J P Desager; M Klánová; M de Longueville; C Harvengt Journal: Clin Pharmacol Ther Date: 1997-03 Impact factor: 6.875
Authors: A Pariente-Khayat; E Rey; M C Dubois; F Vauzelle-Kervroedan; G Pons; P D'athis; I I Murat; M E Pinelli; C Saint-Maurice; G Olive Journal: Int J Clin Pharmacol Ther Date: 1995-06 Impact factor: 1.366
Authors: Peter L Bonate; Malidi Ahamadi; Nageshwar Budha; Amparo de la Peña; Justin C Earp; Ying Hong; Mats O Karlsson; Patanjali Ravva; Ana Ruiz-Garcia; Herbert Struemper; Janet R Wade Journal: J Pharmacokinet Pharmacodyn Date: 2016-02-02 Impact factor: 2.745