Tags

Type your tag names separated by a space and hit enter

Population analysis of the pharmacokinetics and pharmacodynamics of seratrodast in patients with mild to moderate asthma.
Clin Pharmacol Ther. 1997 Oct; 62(4):426-35.CP

Abstract

BACKGROUND

Seratrodast, a potent thromboxane receptor antagonist, is approved in Japan for the treatment of asthma and currently is being developed in the United States.

METHODS

This was a phase II, randomized, double-blind, parallel-group, placebo-controlled 15-center study of seratrodast in patients with mild to moderate asthma. A total of 183 patients were randomly assigned to receive daily doses of either placebo, or 80 mg seratrodast, or 120 mg seratrodast for 8 weeks. Pharmacokinetic and pharmacodynamic modeling was carried out by means of the population approach. A two-compartment model with zero-order input and first-order elimination best fitted the plasma concentration-time data.

RESULTS AND CONCLUSIONS

The pharmacokinetics of seratrodast were linear after single and multiple dosing for 8 weeks. The population estimates for oral clearance and apparent volume of distribution were 8.5 ml/hr/kg and 43.3 ml/kg, respectively. All pharmacokinetic parameters (the oral central compartment clearance, the volumes of distribution of the central and peripheral compartments, and the intercompartmental clearance) were estimated with a precision of 10% or less and were found to be associated with body weight. The residual variability was 30%. The values of oral clearance estimated in this study in male patients were similar to those previously estimated in healthy male subjects. Seratrodast at a dose of 120 mg daily produced an increase in forced expiratory volume in 1 second (FEV1) from baseline that was linearly correlated with its plasma concentrations. The average slope of the concentration-effect relationship was 0.222% and 0.470% per microgram/ml after single and multiple dosing, respectively. Interpatient variability in response was mainly affected by the initial severity of the disease. A lower percentage of predicted FEV1 (i.e., more severe obstruction) was associated with higher slopes, and greater increases in FEV1.

Authors+Show Affiliations

Abbott Laboratories, Abbott Park, IL, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9357394

Citation

Samara, E, et al. "Population Analysis of the Pharmacokinetics and Pharmacodynamics of Seratrodast in Patients With Mild to Moderate Asthma." Clinical Pharmacology and Therapeutics, vol. 62, no. 4, 1997, pp. 426-35.
Samara E, Cao G, Locke C, et al. Population analysis of the pharmacokinetics and pharmacodynamics of seratrodast in patients with mild to moderate asthma. Clin Pharmacol Ther. 1997;62(4):426-35.
Samara, E., Cao, G., Locke, C., Granneman, G. R., Dean, R., & Killian, A. (1997). Population analysis of the pharmacokinetics and pharmacodynamics of seratrodast in patients with mild to moderate asthma. Clinical Pharmacology and Therapeutics, 62(4), 426-35.
Samara E, et al. Population Analysis of the Pharmacokinetics and Pharmacodynamics of Seratrodast in Patients With Mild to Moderate Asthma. Clin Pharmacol Ther. 1997;62(4):426-35. PubMed PMID: 9357394.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Population analysis of the pharmacokinetics and pharmacodynamics of seratrodast in patients with mild to moderate asthma. AU - Samara,E, AU - Cao,G, AU - Locke,C, AU - Granneman,G R, AU - Dean,R, AU - Killian,A, PY - 1997/11/14/pubmed PY - 1997/11/14/medline PY - 1997/11/14/entrez SP - 426 EP - 35 JF - Clinical pharmacology and therapeutics JO - Clin. Pharmacol. Ther. VL - 62 IS - 4 N2 - BACKGROUND: Seratrodast, a potent thromboxane receptor antagonist, is approved in Japan for the treatment of asthma and currently is being developed in the United States. METHODS: This was a phase II, randomized, double-blind, parallel-group, placebo-controlled 15-center study of seratrodast in patients with mild to moderate asthma. A total of 183 patients were randomly assigned to receive daily doses of either placebo, or 80 mg seratrodast, or 120 mg seratrodast for 8 weeks. Pharmacokinetic and pharmacodynamic modeling was carried out by means of the population approach. A two-compartment model with zero-order input and first-order elimination best fitted the plasma concentration-time data. RESULTS AND CONCLUSIONS: The pharmacokinetics of seratrodast were linear after single and multiple dosing for 8 weeks. The population estimates for oral clearance and apparent volume of distribution were 8.5 ml/hr/kg and 43.3 ml/kg, respectively. All pharmacokinetic parameters (the oral central compartment clearance, the volumes of distribution of the central and peripheral compartments, and the intercompartmental clearance) were estimated with a precision of 10% or less and were found to be associated with body weight. The residual variability was 30%. The values of oral clearance estimated in this study in male patients were similar to those previously estimated in healthy male subjects. Seratrodast at a dose of 120 mg daily produced an increase in forced expiratory volume in 1 second (FEV1) from baseline that was linearly correlated with its plasma concentrations. The average slope of the concentration-effect relationship was 0.222% and 0.470% per microgram/ml after single and multiple dosing, respectively. Interpatient variability in response was mainly affected by the initial severity of the disease. A lower percentage of predicted FEV1 (i.e., more severe obstruction) was associated with higher slopes, and greater increases in FEV1. SN - 0009-9236 UR - https://www.unboundmedicine.com/medline/citation/9357394/Population_analysis_of_the_pharmacokinetics_and_pharmacodynamics_of_seratrodast_in_patients_with_mild_to_moderate_asthma_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0009-9236&date=1997&volume=62&issue=4&spage=426 DB - PRIME DP - Unbound Medicine ER -