Excretion of cefprozil into human breast milk

Abstract

The excretion of cefprozil into breast milk in nine healthy, lactating female subjects was investigated. Each subject received a single 1,000-mg oral dose of cefprozil consisting ofcis and tramns isomers in an approximately 90:10 ratio. Serial blod, urine, and breast milk samples were collected and analyzed for the concentrations of the cis and trns isomers by a specific high-pressure liquid chromatography-UV assay. The mean pharmacokinetic parameters for both isomers were essentialy the same. The mean peak concentrations in plasma for the cis isomer were 14.8 Fg/ml, and the area under the concentration curve was 54.8 ,ug* h/mi. The mean values of elimination half-life, renal clearance, and urinary excretion for the cis isomer were 1.69 h, 164 mI/min, and 60%, respectively. The mean concentrations in milk of the cis isomer over a 24-h period ranged from 0.25 to 3.36 pg/ml, with the maximum concentration appearing at 6 h after dosing. The average mamum concentration in milk of the twas isomer was less than 0.26 pg/ml. The concentrations of the twans isomer in plasma and in breast milk were about 1/10 of those for the cis isomer. Less than 0.3% of the dose was excreted in breast milk for both isomers of cefprozil. Even if one assumes that the concentration of cefprozil in milk remains constant at 3.36 pig/ml (the highest concentration of cefprozil observed in breast milk), an infant ingesting an average of 800 ml of milk per day will be exposed to a maximum amount of about 3 mg of cefprozfl per day. This value represents about 0.3% of the maternal dose. Low excretion of cefprozil in breast milk and the excellent safety profile of cefprozil suggest that this cephalosporin may be administered to nursing mothers when indicated.Cefprozil is an oral cephalosporin consisting of cis and trans isomers in an approximately 90:10 ratio. The structure is similar to that of other oral cephalosporins with a propenyl side chain. Cefprozil has a broad antimicrobial spectrum. It is reported to be more active than cefaclor and cephalexin against streptococci, Listeria monocytogenes, and Hae-

HPLC determination of cefprozil in tablets using monolithic and C18 silica columns

“…Although LOD and LOQ of described method cannot be evaluated as much better than the LC‐MS method reported by Wang et al 27, our results were better than almost all of the previously published studies including some LC‐MS methods 19, 20, 24, 28. LOD and LOQ were reported between 0.05 and 20 μg/mL in the previous studies, whereas proposed method allowed about 0.03 and 0.09 μg/mL, respectively.…”

“…The explanation of this improvement was associated to the very low noise of the assays (about 0.25–0.50 mAU), which was interpreted as a total result of acetonitrile usage in mobile phase, high absorptivity of CPZ at 200 nm and avoiding use of buffers to maintain pH. In addition, literature search shows that 245 nm 31, 254 nm 24, and 280 nm 19, 20, 22, 25, 28–30 wavelengths were mainly preferred in UV‐based detections of CPZ. Method development studies exhibited that CPZ absorbs UV light about 79% less at 245 nm, 81% less at 254 nm, and 70% less at 280 nm when compared with 200 nm (Fig.…”

“…Being mostly focused on bioavailability and bioequivalency, the reported assays describe quantitative determination of CPZ in biological fluids such as breast milk 19, plasma 20, and middle ear fluid 21, 22, and in some pharmaceutical preparations such as tablets 23, 24 and oral suspensions 25. Within the methods used to determine CPZ, LC with MS 26–28 or UV 19, 20, 22, 24–25, 28–31 detection was popular. Among these, MS detection shows its superiority over UV detection in terms of specificity and detection limits because of unique capabilities such as multiple and selected reaction monitoring.…”

Analysis and Prediction of Drug Transfer into Human Milk Taking into Consideration Secretion and Reuptake Clearances across the Mammary Epithelia

“…In a recent report, a population-based pharmacokinetic approach was applied to estimate the fluoxetine milk-to-plasma ratio and the exposure of infants to this drug through breast milk, assuming that plasma and milk drug concentrations are roughly parallel (Panchaud et al, 2011). However, the time course of drug concentrations in plasma and milk does not usually increase or decrease in parallel (Somogyi and Gugler, 1979;Shyu et al, 1992), and in these cases, the drug profiles cannot be explained by rapid equilibration. Further improvement of the predictive model to estimate the time profiles of drug concentrations in milk would be useful to minimize the exposure of breast feeding infants to drugs.…”

Antibiotics and Breast-Feeding

“…[72,73,76,[78][79][80][81] In contrast, Blanco et al [40] observed measurable ceftazidime milk concentrations of 3.8 to 8.2 mg/L in the milk of 11 breast-feeding women who were administered ceftazidime 2g intravenously three times daily for 5 days. [72,73,76,[78][79][80][81] In contrast, Blanco et al [40] observed measurable ceftazidime milk concentrations of 3.8 to 8.2 mg/L in the milk of 11 breast-feeding women who were administered ceftazidime 2g intravenously three times daily for 5 days.…”