Elderly Patients Taking Doripenem Do Not Require Dose Adjustment: Presented at AACP

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Title: Elderly Patients Taking Doripenem Do Not Require Dose Adjustment: Presented at AACP
URL: http://www.pslgroup.com/dg/22CA02.htm
Doctor's Guide
September 17, 2008

By Maggie Schwarz

PHILADELPHIA -- September 17, 2008 -- Renal clearance of doripenem is the same in the elderly as it is in patients with mild renal impairment, and therefore no dose adjustment is needed, according to research presented here at the American College of Clinical Pharmacology (ACCP) 37th Annual Meeting.

Nicole Vaccaro, BS, Johnson and Johnson Pharmaceutical Research and Development, Raritan, New Jersey, reported on a study of the effects of age and gender on doripenem pharmacokinetics.

The complexities of treating elderly patients are greater than those of treating younger patients due to increased sensitivity to drug effects, decreased renal clearance, and increased likelihood of concomitant diseases and polypharmacy common to older patients. Since both age and gender may alter the pharmacokinetics of a drug, it is important to investigate the effects of these covariates on drug disposition.

Doripenem is a new carbapenem antibacterial agent approved in the United States and the European Union for treatment of complicated intra-abdominal and urinary tract infections, including pyelonephritis.

In their open-label, single-centre study, Vaccaro and colleagues enrolled 12 patients a median of 19 years old and 12 patients a median of 73 years old. The younger group women were matched by mean body weight to the elderly patients. This study consisted of 3 phases: a 21-day screening phase; a 1-day, open-label treatment phase; and a 7-day post-treatment phase.

The primary pharmacokinetic parameters analysed were area under the curve (AUC) and maximum plasma concentration (C_max) of doripenem. Safety was evaluated by examining incidence, severity, relationship to study drug, types of adverse events, changes in clinical laboratory test results, physical examination results, and vital sign measurements.

Doripenem AUC and C_max in women were both higher (<15%) than the respective values in men. These small differences in the pharmacokinetics of doripenem between men and women were not attributed to body size when body weight was taken into consideration. Therefore, no dosage adjustment is recommended based on gender, the researchers said.

AUC, C_max, and half-life of doripenem were 49%, 23%, and 53% higher, respectively, in the elderly patient group compared with the younger subjects. The differences were mainly attributable to age-related changes in renal function, the researchers said. The increase in exposure to doripenem by the elderly population is similar to that reported for subjects with mild renal impairment, for which no dosage adjustments are recommended, they explained.

The increased doripenem exposure in the elderly was primarily due to an age-related decline in renal function and to a lesser extent in doripenem metabolism, Vaccaro said. The small difference in exposure between men and women was not clinically significant, she added.

Doripenem 500 mg administered intravenously in a single 1-hour infusion appeared to be safe and equally well tolerated by elderly and non-elderly subjects based on adverse event profiles and clinical assessment findings, the researchers concluded.

No doripenem dose adjustment is recommended in elderly subjects with normal renal function or on the basis of gender, they added.

[Presentation title: Effects of Age and Gender on Doripenem Pharmacokinetics. Abstract 45]

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