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Prospective, Controlled Study of Acyclovir Pharmacokinetics in Obese Patients. Antimicrob Agents Chemother 2016 Jan 11;60(3):1830-3

Date

01/30/2016

Pubmed ID

26824940

Pubmed Central ID

PMC4775958

DOI

10.1128/AAC.02010-15

Scopus ID

2-s2.0-84960387281 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

The current recommendations for intravenous (i.v.) acyclovir dosing in obese patients suggest using ideal body weight (IBW) rather than total body weight (TBW). To our knowledge, no pharmacokinetic analysis has validated this recommendation. This single-dose pharmacokinetic study was conducted in an inpatient oncology population. Enrollment was conducted by 1:1 matching of obese patients (>190% of IBW) to normal-weight patients (80 to 120% of IBW). All patients received a single dose of i.v. acyclovir, 5 mg/kg, infused over 60 min. Consistent with current recommendations, IBW was used for obese patients and TBW for normal-weight patients. Serial plasma concentrations were obtained and compared. Seven obese and seven normal-weight patients were enrolled, with mean body mass indexes of 45.0 and 22.5 kg/m(2), respectively. Systemic clearance was substantially higher in the obese than normal-weight patients (mean, 19.4 ± 5.3 versus 14.3 ± 5.4 liters/h; P = 0.047). Area under the concentration-time curve was lower in the obese patients (15.2 ± 2.9 versus 24.0 ± 9.4 mg · h/liter; P = 0.011), as was maximum concentration (5.8 ± 0.9 versus 8.2 ± 1.3 mg/liter; P = 0.031). Utilization of IBW for dose calculation of i.v. acyclovir in obese patients leads to lower systemic exposure than dosing by TBW in normal-weight patients. While not directly evaluated in this study, utilization of an adjusted body weight for dose determination appears to more closely approximate the exposure seen in normal-weight patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01714180.).

Author List

Turner RB, Cumpston A, Sweet M, Briggs F, Slain D, Wen S, Craig M, Hamadani M, Petros W

Author

Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acyclovir
Body Mass Index
Drug Dosage Calculations
Female
Humans
Ideal Body Weight
Male
Middle Aged
Obesity
Prospective Studies