Amoxicillin pharmacokinetics in pregnant women: modeling and simulations of dosage strategies.
Amoxicillin is recommended for anthrax prevention in pregnancy. The objective of this study was to evaluate the pharmacokinetics of amoxicillin during pregnancy and postpartum (PP). Sixteen women received amoxicillin during gestation (18-22 weeks (T2) and 30-34 weeks (T3)) as well as 3 months postpartum (PP) to evaluate single-dose pharmacokinetics. Amoxicillin compartmental pharmacokinetic parameters were used to simulate amoxicillin concentration-time profiles following different dosage strategies. Amoxicillin CL(renal) (T2: 24.8+/-6.7 l/h, P<0.001; T3: 24.0+/-3.9 l/h, P<0.001; and PP: 15.3+/-2.6 l/h) and renal CL(secretion) (T2: 280+/-105 ml/min, P<0.002; T3: 259+/-54 ml/min, P<0.001; and PP: 167+/-47 ml/min) were higher during pregnancy than postpartum. Simulations suggest that amoxicillin concentrations adequate to prevent anthrax may be difficult to achieve during pregnancy and postpartum. Increases in amoxicillin CL(renal) and renal CL(secretion) reflect increases in filtration and secretory transport or diminished reabsorption in the kidneys. Amoxicillin may not be an appropriate antibiotic for post-anthrax exposure prophylaxis.
Andrew
M A
MA
Department of Bioengineering, University of Washington, Seattle, Washington, USA.
Easterling
T R
TR
Carr
D B
DB
Shen
D
D
Buchanan
M L
ML
Rutherford
T
T
Bennett
R
R
Vicini
P
P
Hebert
M F
MF
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000658:Amoxicillin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008875:Middle Aged; D015233:Models, Statistical; D009010:Monte Carlo Method; D010406:Penicillins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011247:Pregnancy / Q000378:metabolism*; D011262:Pregnancy Trimester, Second / Q000378:metabolism; D011263:Pregnancy Trimester, Third / Q000378:metabolism
D010406:Penicillins; D000658:Amoxicillin