title: Prospective, Controlled Study of Acyclovir Pharmacokinetics in Obese Patients.
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.).
authors.affiliation: West Virginia University Healthcare, Morgantown, West Virginia, USA.
authors.forename: R Brigg
authors.initials: RB
authors.lastname: Turner
authors.affiliation: West Virginia University Healthcare, Morgantown, West Virginia, USA Mary Babb Randolph Cancer Center, Morgantown, West Virginia, USA cumpstona@wvuhealthcare.com.
authors.forename: Aaron
authors.initials: A
authors.lastname: Cumpston
authors.affiliation: West Virginia University Healthcare, Morgantown, West Virginia, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Sweet
authors.affiliation: West Virginia University Healthcare, Morgantown, West Virginia, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Briggs
authors.affiliation: West Virginia University Healthcare, Morgantown, West Virginia, USA West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Slain
authors.affiliation: Mary Babb Randolph Cancer Center, Morgantown, West Virginia, USA West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Sijin
authors.initials: S
authors.lastname: Wen
authors.affiliation: Mary Babb Randolph Cancer Center, Morgantown, West Virginia, USA West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Craig
authors.affiliation: Mary Babb Randolph Cancer Center, Morgantown, West Virginia, USA West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hamadani
authors.affiliation: Mary Babb Randolph Cancer Center, Morgantown, West Virginia, USA West Virginia University, Morgantown, West Virginia, USA.
authors.forename: William
authors.initials: W
authors.lastname: Petros
mesh_terms: D000212:Acyclovir / Q000097:blood* / Q000493:pharmacokinetics*; D015992:Body Mass Index; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D056865:Ideal Body Weight; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D011446:Prospective Studies
chemical_list: D000212:Acyclovir
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