Influence of morbid obesity on the single-dose pharmacokinetics of daptomycin.
The present study characterized the single-dose pharmacokinetics of daptomycin dosed as 4 mg/kg of total body weight (TBW) in seven morbidly obese and seven age-, sex-, race-, and serum creatinine-matched healthy subjects. The glomerular filtration rate (GFR) was measured for both groups following a single bolus injection of [(125)I]sodium iothalamate. Noncompartmental analysis was used to determine the pharmacokinetic parameters, and these values were normalized against TBW, ideal body weight (IBW), and fat-free weight (FFW) for comparison of the two groups. All subjects enrolled in this study were female, and the mean (+/-standard deviation) body mass index was 46.2 +/- 5.5 kg/m(2) or 21.8 +/- 1.9 kg/m(2) for the morbidly obese or normal-weight group, respectively. The maximum plasma concentration and area under the concentration-time curve from dosing to 24 h were approximately 60% higher (P < 0.05) in the morbidly obese group than in the normal-weight group, and these were a function of the higher total dose received in the morbidly obese group. No differences in daptomycin volume of distribution (V), total clearance, renal clearance, or protein binding were noted between the two groups. Of TBW, FFW, or IBW, TBW provided the best correlation to V. In contrast, TBW overestimated GFR through creatinine clearance calculations using the Cockcroft-Gault equation. Use of IBW in the Cockcroft-Gault equation or use of the four-variable modification of diet in renal disease equation best estimated GFR in morbidly obese subjects. Further studies of daptomycin pharmacokinetics in morbidly obese patients with acute bacterial infections and impaired renal function are necessary to better predict appropriate dosage intervals.
Pai
Manjunath P
MP
College of Pharmacy, MSC09 5360, 1 University of New Mexico, Albuquerque, NM 87131-0001, USA. apai@salud.unm.edu
Norenberg
Jeffrey P
JP
Anderson
Tamara
T
Goade
Diane W
DW
Rodvold
Keith A
KA
Telepak
Robert A
RA
Mercier
Renee-Claude
RC
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000652:urine; D015992:Body Mass Index; D001835:Body Weight; D017576:Daptomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism
D000900:Anti-Bacterial Agents; D017576:Daptomycin