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By Imam Hussain Shaik

Imam Hussain Shaik-finalObesity has become a major epidemic in the United States irrespective of age, gender, or race. This condition has a major influence on an individual’s health status, and contributes to multiple disease conditions, and is an independent risk factor for the development of postoperative surgical site infections.

Pregnant women undergoing caesarian delivery typically receive cefazolin, a cephalosporin antibiotic. To be an effective prophylactic agent, cefazolin concentration must exceed the minimum inhibitory concentration for gram-positive cocci of 1 µg/gm and gram-negative rods (GNRs) of 4 µg/gm in the target tissue. The American Congress of Obstetricians and Gynecologists recommend administration of 2 gm of cefazolin within 60 min of skin incision. The primary research question was if this dose is sufficient in obese pregnant women undergoing a caesarian section. This is especially important given that pregnancy is known to increase elimination of drugs like cefazolin.

At the upcoming 2015 AAPS Annual Meeting and Exposition, I will present my work performed in Raman Venkatramanan’s lab in collaboration with Omar Young and Steve Caritis from Magee Women’s Hospital, Pittsburgh. We compared the plasma and tissue concentration profiles of cefazolin after 2 or 3 gm in obese pregnant women at the time of caesarian delivery. The overall maternal exposure and adipose tissue levels were increased with increase in dose, but there were no changes in the pharmacokinetic parameters such as volume of distribution, clearance, and half-life. The generalized linear modeling of the observed plasma concentrations indicate that body mass index affects the maternal plasma exposure of cefazolin (Figure 1). However, both 2 and 3 gm dose achieved concentrations of cefazolin in the adipose tissues above the minimum inhibitory concentrations. A dose of 2 gm appears to be sufficient even in obese pregnant women.

It is important to understand the physicochemical and pharmacokinetic properties of drugs in order to rationalize changes in dosing requirements of drugs in obese subjects. This study also points out that changes in plasma exposure need not imply need for changes in drug dosing, as long as therapeutic drug concentrations are achieved in target tissues.

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Figure 1

Imam Hussain Shaik, Ph.D., is a postdoctoral fellow in laboratory of Raman Venkataramanan at School of Pharmacy, University of Pittsburgh.