Population pharmacokinetics of pranlukast hydrate dry syrup in children with bronchial asthma

Background: This is the first report about the pharmacokinetics (PK) of pranlukast in children. The aim of the present study was to assess the PK parameters of pranlukast in children and to compare them with those in adults. Methods: Six healthy adult male volunteers and 22 children with bronchial asthma at 3–14 years of age were enrolled in the study. Both 225 and 112.5 mg pranlukast hydrate dry syrup was administered orally to adults, whereas 3.5 mg/kg pranlukast hydrate dry syrup was given to children. Blood samples were obtained at approximately 20 time points per adult (n=121) and at two or three time points per child (n=54). Population PK analysis was performed using NONMEM (Globomax, Hanover, MD, USA). The concentration-time-course of pranlukast was described by using a one-compartment model with first-order absorption. The robustness of the final model was evaluated using 200 bootstrap samples. Results: Apparent clearance (CL/F) was 1.81 and 1.14 L/h per kg in children and adults, respectively. According to subgrouping of children, no significant difference was observed in CL/F between infants (3–6 years of age) and schoolchildren (7–14 years of age). The interindividual variability of CL/F accounted for 48.7%. The additive and proportional residual variability was 7.33 ng/mL and 73.8%, respectively. All fixed effect parameters fell within 10% of the bootstrapped mean. Conclusions: Compared with adults, children showed a higher CL/F and more rapid elimination after ingestion of pranlukast hydrate dry syrup. However, no significant variation was seen in CL/F between infants and schoolchildren

Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in patients with peripheral arterial disease.

出版社版 オープンアクセス CC BY-NCPURPOSE: We previously determined the pharmacokinetic (PK) parameters of landiolol in healthy male volunteers and gynecological patients. In this study, we determined the PK parameters of landiolol in patients with peripheral arterial disease. METHODS: Eight patients scheduled to undergo peripheral arterial surgery were enrolled in the study. After inducing anesthesia, landiolol hydrochloride was administered at target plasma concentrations of 500 and 1,000 ng/mL for 30 minutes each. A total of 112 data points of plasma concentration were collected from the patients and used for the population PK analysis. A population PK model was developed using a nonlinear mixed-effect modeling software program (NONMEM). RESULTS: The patients had markedly decreased heart rates at 2 minutes after initiation of landiolol hydrochloride administration; however, systolic blood pressures were lower than the baseline values at only five time points. The concentration time course of landiolol was best described by a two-compartment model with lag time. The estimates of PK parameters were as follows: total body clearance, 30.7 mL/min/kg; distribution volume of the central compartment, 65.0 mL/kg; intercompartmental clearance, 48.3 mL/min/kg; distribution volume of the peripheral compartment, 54.4 mL/kg; and lag time, 0.633 minutes. The predictive performance of this model was better than that of the previous model. CONCLUSION: The PK parameters of landiolol were best described by a two-compartment model with lag time. Distribution volume of the central compartment and total body clearance of landiolol in patients with peripheral arterial disease were approximately 64% and 84% of those in healthy volunteers, respectively

Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in gynecologic patients.

PURPOSE: We previously determined the pharmacokinetic (PK) parameters of landiolol in healthy male volunteers. In this study, we evaluated the usefulness of target-controlled infusion (TCI) of landiolol hydrochloride and determined PK parameters of landiolol in gynecologic patients. METHODS: Nine patients who were scheduled to undergo gynecologic surgery were enrolled. After inducing anesthesia, landiolol hydrochloride was administered at the target plasma concentrations of 500 and 1,000 ng/mL for each 30 min. A total of 126 data points of plasma concentration were collected from the patients and used for the population PK analysis. Furthermore, a population PK model was developed using the nonlinear mixed-effect modeling software. RESULTS: The patients had markedly decreased heart rates (HRs) at 2 min after the initiation of landiolol hydrochloride administration; however, their blood pressures did not markedly change from the baseline value. The concentration time course of landiolol was best described by a 2-compartment model with lag time. The estimate of PK parameters were total body clearance (CL) 34.0 mL/min/kg, distribution volume of the central compartment (V 1) 74.9 mL/kg, inter-compartmental clearance (Q) 70.9 mL/min/kg, distribution volume of the peripheral compartment (V 2) 38.9 mL/kg, and lag time (ALAG) 0.634 min. The predictive performance of this model was better than that of the previous model. CONCLUSION: TCI of landiolol hydrochloride is useful for controlling HR, and the PK parameters of landiolol in gynecologic patients were similar to those in healthy male volunteers and best described by a 2-compartment model with lag time