Pharmacokinetics and Drug Disposition
Clinical Pharmacology & Therapeutics (2006) 79, 114–124; doi: 10.1016/j.clpt.2005.09.007
Population analyses of amlodipine in patients living in the community and patients living in nursing homes*
Dongwoo Kang PhD1,2, Davide Verotta PhD1,2 and Janice B. Schwartz MD1,2
- 1Departments of Medicine and Biopharmaceutical Sciences, Division of Clinical Pharmacology, University of California, and Jewish Home of San Francisco, San Francisco
- 2ALZA, Mountain View, Calif
Correspondence: Janice B. Schwartz, MD, 302 Silver Ave, San Francisco, CA 94112 E-mail: jbsucsf@itsa.ucsf.edu
*This study was funded in part by grants R01 AG15982 and Al50587 from the National Institutes of Health and carried out in part at the General Clinical Research Center, Moffitt Hospital, University of California, San Francisco (San Francisco, Calif), with funds provided by the National Center for Research Resources (5 M01 RR-00079), US Public Health Service.
Received 8 July 2005; Accepted 7 September 2005.
Abstract
Objective: Our objective was to determine the effects of age, sex, and morbidity on the apparent oral clearance (CL/F) of amlodipine.
Methods: Population pharmacokinetic analyses were performed on data from 211 patients receiving oral racemic amlodipine (dose of 7.2
3.6 mg/d [meanSD]) on a long-term basis. Of the patients, 105 were men, with a mean age of 7213 years and lean body weight (LBW) of 60.77.6 kg, and 106 were women, with a mean age of 7911 years and LBW of 44.26.0 kg; 119 lived in the community, 20 in assisted living facilities, and 72 in nursing homes. Amlodipine was measured by liquid chromatography–tandem mass spectrometry. Population analyses were performed by use of NONMEM with sex, age, race, living site, alcohol intake, and concomitant medications considered as covariates. The significance of covariates was determined by likelihood ratio tests.
Results: Female sex and living in a nursing home were associated with a faster CL/F compared with men and community-dwelling patients, respectively. The mean CL/F was 7.830.50 mL
min-1kg-1 (LBW) in women compared with 6.311.01 in men and 8.681.00 mLmin-1kg-1 in nursing home residents compared with 6.321.17 in community-dwelling patients. Increasing age was associated with decreasing CL/F only in community-dwelling patients and residents of assisted living facilities.
Conclusions: In middle-aged and very old (>80 years) patients, amlodipine CL/F was faster in women compared with men and was faster in nursing home residents compared with community-dwelling patients, with increasing age decreasing CL/F only in community-dwelling patients and residents of assisted-living facilities.
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