Biomedical subjects

K A Pittman

Publications and source records attributed to K A Pittman.

At least 37 records · Page 2Linked to original sources

PubMed1992

Lack of pharmacokinetic interaction between cefepime and amikacin in humans.

The interaction potential between cefepime and amikacin was investigated in a steady-state pharmacokinetic study in 16 healthy male subjects. Eight subjects (group A) received a first course of 2,000 mg of cefepime; this was followed by a second course of 2,000 mg of cefepime with 300 mg of amikacin and a third course of 2,000 mg of cefepime. Eight other subjects (group B) received a first course of 300 mg of amikacin, a second course of 300 mg of amikacin with 2,000 mg of cefepime, and a third course of 300 mg of amikacin. Each course consisted of four consecutive doses administered every 8 h as 30-min intravenous infusions. Serial plasma and urine samples, which were collected after administration of the fourth dose of each course, were assayed for cefepime and/or amikacin by validated high-performance liquid chromatographic assays. Trough levels of cefepime and amikacin indicated that these antibiotics attained a steady state prior to administration of the fourth dose of each course. Key pharmacokinetic parameters for each antibiotic were determined by noncompartmental methods. The peak concentrations of cefepime and amikacin in plasma when the drugs were given alone were about 160 and 27 micrograms/ml, respectively. Levels of each antibiotic in plasma declined, with an apparent half-life of approximately 2.2 h. Urinary recovery of cefepime and amikacin accounted for more than 85% of the administered dose of each antibiotic. Mean renal clearances for cefepime and amikacin ranged from 79 to 95 ml/min and suggested that glomerular filtration is the primary excretion mechanism. The results of the statistical analyses indicated that the pharmacokinetic parameters of cefepime following the concurrent administration of amikacin and following the discontinuation of the amikacin following the concurrent administration of cefepime and following the discontinuation of the cefepime therapy were not significantly altered. Cefepime and amikacin can be coadministered to patients with normal renal function by using the standard recommended dosing regimens.

Adult↗

PubMed1992

Pharmacokinetics of cefepime in patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of cefepime were studied in 10 male patients receiving continuous ambulatory peritoneal dialysis therapy. Five patients received a single 1,000-mg dose and the other five received a single 2,000-mg dose; all doses were given as 30-min intravenous infusions. Serial plasma, urine, and peritoneal dialysate samples were collected; and the concentrations of cefepime in these fluids were measured over 72 h by using a high-performance liquid chromatographic assay with UV detection. Pharmacokinetic parameters were calculated by noncompartmental methods. The peak concentrations in plasma and the areas under the plasma concentration-versus-time curve for the 2,000-mg dose group were twice as high as those observed for the 1,000-mg dose group. The elimination half-life of cefepime was about 18 h and was independent of the dose. The steady-state volume of distribution was about 22 liters, and values for the 1,000- and 2,000-mg doses were not significantly different. The values for total body clearance and peritoneal dialysis clearance were about 15 and 4 ml/min, respectively. No dose dependency was observed for the clearance estimates. Over the 72-h sampling period, about 26% of the dose was excreted intact into the peritoneal dialysis fluid. For 48 h postdose, mean concentrations of cefepime in dialysate at the end of each dialysis interval exceeded the reported MICs for 90% of the isolates (MIC90s) for bacteria which commonly cause peritonitis resulting from continuous peritoneal dialysis. A parenteral dose of 1,000 or 2,000 mg of cefepime every 48 h would maintain the antibiotic levels in plasma and peritoneal fluid above the MIC90s for the most susceptible bacteria for the treatment of systemic and intraperitoneal infections [corrected].

Cefepime↗

PubMed1991

High-performance liquid chromatographic method for the determination of nefazodone and its metabolites in human plasma using laboratory robotics.

A quantitative analytical method, using high-performance liquid chromatography and ultraviolet detection, has been established for the determination of nefazodone (NEF) and its metabolites, m-chlorophenylpiperazine (mCPP),p-hydroxynefazodone (PHN), and hydroxynefazodone (HO-NEF), in human plasma. The fully automated, robotic procedure consisted of addition of internal standard (aprindine), extraction with butyl chloride, followed by phase separation, organic phase evaporation, reconstitution of the residue, and injection onto the chromatographic system. The limits of detection for NEF, mCPP, PHN, and HO-NEF were 5, 1, 10, and 5 ng/ml, respectively, at a signal-to-noise ratio of 4. The method had a linear range of 10-1000 ng/ml for NEF and HO-NEF, 20-2000 ng/ml for PHN, and 2.5-250 ng/ml for mCPP. Correlation coefficients of 0.996 or greater were obtained during validation and study sample analysis.

Adolescent↗

PubMed1991

High-performance liquid chromatographic assay of alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY 14802), a potential antipsychotic drug, in monkey and rat plasma.

A high-performance liquid chromatographic-fluorescence method was developed for the quantitative analysis of BMY-14802 (I) in monkey and rat plasma. After the addition of the internal standard (BMY-14853 I.S.), 250 microliters of plasma were made basic by the addition of 2 ml of saturated sodium carbonate buffer. Compound I and the I.S. were then extracted into 5 ml of methyl tert.-butyl ether. The organic phase was evaporated and the resulting residue was reconstituted in mobile phase. Final separation and quantitation of I was achieved on an octadecyl column with a 0.05 M potassium phosphate-acetonitrile-triethylamine-85% phosphoric acid (650:350:0.1:0.05, v/v) mobile phase. Fluorescence detection was used to monitor the eluent at an excitation wavelength of 240 nm and an emission wavelength of 400 nm. The limit of detection was 0.5 ng/ml. The standard curve was linear over the range 5.0-1000 ng/ml. Intra-assay and inter-assay precision values were less than 4.0% relative standard deviation and accuracy was within 12% of nominal values. Compound I was shown to be stable in monkey and rat plasma for at least six months when stored at -20 degrees C.

Animals↗

PubMed1991

Pharmacokinetics of cefprozil in healthy subjects and patients with renal impairment.

Cefprozil, a new broad-spectrum oral cephalosporin, is composed of cis and trans isomers in an approximate 90:10 ratio. The pharmacokinetics of a single oral 1000-mg dose of cefprozil were evaluated in 6 healthy subjects and 24 patients with various degrees of renal impairment. Six of these subjects were studied both while receiving hemodialysis and during an interdialytic period. Plasma, urine, and hemodialysate that were collected at predetermined times were analyzed for concentrations of the cis and trans isomers of cefprozil using reverse-phase HPLC assay with UV detection. The maximum plasma concentration of the cis isomer ranged from 12.3 micrograms/mL in subjects with normal renal function to 36.7 micrograms/mL in hemodialysis patients. Similarly the area under the plasma concentration-time curve and the elimination half-life increased from 46 micrograms.h/mL to 373 micrograms.h/mL and from 1.72 hours to 5.94 hours, respectively. Renal clearance of the cis isomer decreased from 198 mL/min in normal subjects to 19 mL/min in volunteers with creatinine clearances of less than or equal to 30 mL/min; there was a strong correlation (r2 greater than or equal to .93) between the renal clearance of the cis isomer and creatinine clearance. Urinary recovery of the cis isomer decreased from 57% in those with normal renal function to 24% in the group with a creatinine clearance of less than or equal to 30 mL/min. Hemodialysis decreased the half-life of the cis isomer to 2 hours and removed approximately 55% of it from the body during a 3-hour dialysis period (hemodialysis clearance equaled approximately 87 mL/min). The pharmacokinetics of the trans isomer were similar to those observed for the cis isomer and were affected similarly by declining renal function. A reduction in dosage is recommended in patients with a creatinine clearance of 30 mL/min or less. It may be necessary to administer a dose after hemodialysis to maintain therapeutic plasma concentrations.

Administration, Oral↗

PubMed1991

Pharmacokinetics of cefprozil in healthy subjects and patients with hepatic impairment.

The pharmacokinetics of cefprozil were studied in 12 (9 men, 3 women) subjects with hepatic impairment and in 12 healthy subjects who were matched for age, sex, and weight. Each subject received a single 1000 mg oral dose of cefprozil, which consists of cis and trans isomers in approximately a 90:10 ratio. Serial blood and urine samples were collected and analyzed using validated HPLC/UV methods for the concentration of each isomer. The results of the plasma and urine analyses were subjected to noncompartmental pharmacokinetic analysis. The values for the peak plasma concentrations (Cmax), area under the plasma concentration versus time curve (AUC0-infinity), apparent total body clearance (Clt/F), renal clearance (Clr), and percent of drug excreted in urine (%UR) of each isomer were not significantly different in healthy subjects and patients with hepatic impairment. The only parameters that were significantly (P less than or equal to .05) longer in patients with hepatic impairment were mean residence time in the body (MRT) and half-life; the MRT for the cis isomer in healthy subjects and subjects with hepatic impairment were 3.33 hr and 3.88 hr, respectively, and for the trans isomer 3.17 hr and 3.68 hr; the half-life for the cis isomer was 1.62 hr and 2.22 hr, respectively, and for the trans isomer 1.21 hr and 1.54 hr. The pharmacokinetics of the cis and trans isomers of cefprozil were virtually identical in healthy subjects as well as those with hepatic impairment.

Administration, Oral↗

PubMed1991

Food-induced reduction in bioavailability of didanosine.

The effect of food on the pharmacokinetics of didanosine was evaluated in an open two-way crossover study in eight male subjects who tested seropositive for the human immunodeficiency virus. Each subject received a single 375 mg oral dose of didanosine in a chewable tablet form with or without food. Serial blood samples and the total urinary output during 12 hours were collected and assayed for intact didanosine by validated HPLC methods. The mean (SD) values for the peak concentration (Cmax) of didanosine in plasma were 2789 (1032) ng/ml and 1291 (536) ng/ml and for the area under the plasma concentration-time curves (AUC0-infinity) were 3902 (1316) and 2083 (922) hr.ng/ml, and the urinary excretion (%UR) accounted for 21% and 11% of dose as intact didanosine when didanosine was given under fasting conditions and with food, respectively. The values of Cmax, AUC0-infinity, and %UR were significantly lower for subjects who received didanosine with food compared with those observed for the fasted subjects. The time to reach Cmax, mean residence time, elimination half-life, and renal clearance remained essentially the same between the two treatments. The results from this study indicated that the rates of absorption and elimination were not affected by the presence of food; however, the extent of absorption, as indicated by AUC0-infinity and %UR, was reduced significantly in the presence of food. It is recommended that didanosine be administered under fasting conditions.

Administration, Oral↗

PubMed1991

Pharmacokinetics of didanosine in patients with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome-related complex.

The pharmacokinetics of didanosine (2',3'-dideoxyinosine) after intravenous and oral administration were evaluated in an open, escalating-dose phase I study in patients with acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex. Didanosine was administered twice a day for 2 weeks as an intravenous infusion of 60 minutes duration at doses ranging from 0.4 to 16.5 mg/kg, followed by 4 weeks of oral treatment at twice the intravenous dose. Serial blood and urine samples were obtained on the first and final day of intravenous administration and after the first oral dose, as well as at steady state. Didanosine demonstrated linear pharmacokinetic behavior over the dose ranges of 0.4 to 16.5 mg/kg intravenously and 0.8 to 10.2 mg/kg orally. There was no indication of significant changes in pharmacokinetic parameters with repeated administration. The apparent elimination half-life after oral administration was approximately 1.4 hour. Renal clearance values exceeded the glomerular filtration rate, indicating that active tubular secretion of didanosine occurs. Bioavailability of didanosine when administered as a solution with an antacid was approximately 43% for doses from 0.8 to 10.2 mg/kg in patients with AIDS and advanced AIDS-related complex. Bioavailability of didanosine from the citrate-phosphate-buffered solution, the formulation currently used in phase II and expanded access studies, was comparable to the formulation used in the phase I trials.

AIDS-Related Complex↗

PubMed1991

Pharmacokinetics of 2',3'-dideoxyinosine (BMY-40900), a new anti-human immunodeficiency virus agent, after administration of single intravenous doses to beagle dogs.

The pharmacokinetics of 2',3'-dideoxyinosine (ddI) were investigated in four adult male beagle dogs that received 15-min infusions of 20-, 50-, and 100-mg/kg doses in a randomized crossover study design. Plasma and urine samples were collected for 10 and 24 h, respectively, and assayed for ddI by high-performance liquid chromatographic methods. The mean maximum concentrations of drug in plasma at the end of 15-min infusions for the 20-, 50-, and 100-mg/kg doses were 33.3, 90.0, and 202 micrograms/ml, respectively. Area under the concentration-time curve data deviated significantly from linearity. The mean total clearance for the low dose (250 ml/min) was significantly greater than that for the high dose (190 ml/min). Renal clearance, which averaged between 98 and 116 ml/min, was dose independent. Renal clearance implied that nonrenal clearance decreased at the high dose (92 ml/min) when compared with that of the low dose (134 ml/min). The average urinary recovery of ddI for the high dose (51.2% of dose) was significantly greater than that for the low dose (45.8%). The volume of distribution at steady state averaged between 7.6 and 10.5 liters and decreased with increasing dose; however, it was not statistically significant. The mean half-life and mean residence time were invariant with respect to dose and averaged between 0.94 and 1.07 h and 0.61 and 0.71 h, respectively. In this dose range, ddI pharmacokinetics are dose dependent.

Animals↗

PubMed1990

Determination of belfosdil, a new calcium channel blocker, in human plasma by capillary gas chromatography with nitrogen-phosphorus detection.

Belfosdil and the internal standard were extracted from human plasma by a double liquid-liquid extraction. After a concentration step, gas chromatographic analysis of the sample was performed using a capillary fused-silica column and a nitrogen-phosphorus detector. The limit of detection of belfosdil was 0.025 ng/ml and the standard curve was linear over the range 0.05-100 ng/ml. The intra-assay and inter-assay precisions were within 7% (relative standard deviation) and the intra-assay and inter-assay accuracy values deviated by less than 5%. The extractability of belfosdil was 79%. The assay method was successfully used for the analysis of plasma samples from clinical studies with dose ranges of 5-100 mg of belfosdil.

Calcium Channel Blockers↗

PubMed1990

Safety, tolerance, and pharmacokinetics of cefepime administered intramuscularly to healthy subjects.

Steady state pharmacokinetics, absolute bioavailability, and dose proportionality of cefepime were evaluated in healthy male subjects after single (250, 500, 1000, or 2000 mg) and multiple (1000 mg every 12 hours for 10 days) intramuscular injections. Safety and tolerance were also monitored. High performance liquid chromatography/UV methodology was used to determine cefepime concentrations in plasma and urine. Key pharmacokinetic parameters were determined using noncompartmental methods. Cefepime was absorbed rapidly; mean peak times were 1.0-1.6 hours. Pharmacokinetics were linear over the 250-mg to 2000-mg dose range, with mean total body clearance ranging from 125 to 141 mL/min. The peak plasma concentration and area under the curve increased in a dose-proportional manner. The apparent elimination half-life (2 hours) did not appear to be influenced by dose or by duration of dosing. No accumulation of cefepime was observed during the multiple-dose study. More than 80% of the administered dose was excreted in the urine as unchanged cefepime, and absolute bioavailability after intramuscular dose was 100%. Cefepime was well tolerated. Most subjects experienced none to mild pain and only minimum discomfort at the site of injection.

Adult↗

PubMed1990

Pharmacokinetics of cefepime in subjects with renal insufficiency.

The pharmacokinetics of intravenously administered cefepime (1000 mg over 30 minutes) were studied in 5 healthy volunteers and 20 patients with various degrees of renal impairment. Cefepime concentrations in plasma, urine, and hemodialysate were assayed using reverse-phase HPLC with ultraviolet detection. Mean peak plasma concentrations of cefepime at the end of 30-minute infusion ranges from 63.5 to 73.9 micrograms/ml and were not affected by the degree of renal impairment. The half-life of cefepime was approximately 2.3 hours in subjects with normal kidney function; it increased proportionately as renal function decreased. Significant linear relationships between total body clearance and creatinine clearance, as well as renal clearance and creatinine clearance, were observed. The mean volume of distribution at steady state in healthy volunteers was 20.5 liters and was not significantly altered in subjects with renal insufficiency. The mean cumulative urinary recovery of cefepime in healthy volunteers was 82.9% of the administered dose and significantly decreased in subjects with creatinine clearance less than 30 ml/min. Hemodialysis significantly shortened the elimination half-life from 13.5 hours during the predialysis period to 2.3 hours during the dialysis period. Cefepime dosage should be reduced in proportion to the decline in creatinine clearance.

Adult↗

PubMed1990

Rapid screening for polymorphisms in dextromethorphan and mephenytoin metabolism.

1. The phenotyping parameters for dextromethorphan and mephenytoin were assessed in 48 normal male volunteers following administration of each metabolic probe drug on separate occasions and together according to a randomized 3-way crossover design. 2. Neither the urinary S-/R-mephenytoin ratio nor the dextromethorphan metabolic ratio were altered significantly by coadministration of the probe drugs. 3. Five-hundred and nineteen subjects were screened for expression of mephenytoin 4-hydroxylase and dextromethorphan O-demethylase activity following the coadministration of mephenytoin and dextromethorphan. The activity was determined in each case by methods not requiring any quantitative measurements. 4. Nineteen (3.7%) of the subjects were identified as poor metabolizers (PMs) of mephenytoin and 35 subjects (6.7%) as PMs of dextromethorphan. 5. All PMs of dextromethorphan were confirmed by more rigorous evaluation of the metabolic ratio.

Adolescent↗

PubMed1990

Phase I study of single-dose BMY-28100, a new oral cephalosporin.

The objective of this Phase I study was to evaluate the safety, tolerance, and pharmacokinetics of BMY-28100 in 36 male subjects after the administration of single oral doses of 250, 500, and 1,000 mg. The subjects were divided into groups of 12 per dose group. All subjects completed the study, and BMY-28100 was well tolerated at all doses. The maximum concentration of the drug in plasma ranged from 6.2 to 17.7 micrograms/ml for the 250- and 1,000-mg doses, respectively, and the area under the curve increased in a dose-proportional manner. The elimination half-life and renal clearance averages were 1.2 h and 200 ml/min, respectively. The values for renal clearance suggest that BMY-28100 is excreted by glomerular filtration and tubular secretion. Mean concentrations of the drug in urine were highest during the first 4 h after the doses and ranged from 175 to 658 micrograms/ml following the 250- and 1,000-mg doses, respectively. The mean urinary recovery ranged from 57 to 70% of the dose. The results from this Phase I study indicate that BMY-28100 is well tolerated and exhibits linear pharmacokinetics.

Adult↗

PubMed1990

Safety, tolerance, and pharmacokinetic evaluation of cefepime after administration of single intravenous doses.

In this double-blind, single-dose phase I study, the safety and tolerance of cefepime were assessed in 24 healthy male subjects, with ceftazidime as the control drug. Four subjects in each of the six dose groups (62.5, 125, 250, 500, 1,000, or 2,000 mg as a 30-min intravenous infusion) received each antibiotic, according to a crossover design, with a 2-day washout period between treatments. Blood and urine samples were obtained to characterize the pharmacokinetics of cefepime. Plasma and urine samples were assayed for intact cefepime. Samples containing ceftazidime were discarded. The adverse effects observed in the study were mild and infrequent, with prompt recovery from adverse experiences and abnormal laboratory values. The cefepime pharmacokinetic parameters for the therapeutically significant doses of 250 to 2,000 mg appeared to be proportional to dose and similar to literature values for ceftazidime. The elimination half-life of about 2 h was independent of the dose. Urinary recovery of intact cefepime was invariant with respect to dose; an overall mean value of 82% of dose was obtained for the four highest levels. Mean renal clearance was 105 ml/min and suggestive of glomerular filtration as the primary excretion mechanism. In normal humans, the safety and pharmacokinetic profiles of cefepime are very similar to those of ceftazidime.

Adult↗

PubMed1990

Phase I study of multiple-dose cefprozil and comparison with cefaclor.

The objectives of this study were to assess the safety and tolerance of cefprozil, to characterize the pharmacokinetics of cefprozil after administration of multiple doses of the drug, and to compare these pharmacokinetic parameters with those obtained with cefaclor. The volunteers received 28 doses of 250, 500, or 1,000 mg of cefprozil or 500 mg of cefaclor every 8 h for 10 days. Serial blood samples and the total volume of urine voided by each individual were collected for pharmacokinetic evaluation on days 1, 5, and 10. Both cephalosporins were well tolerated after multiple oral dosing. The peak levels in plasma (Cmax) of cefprozil ranged from 5.7 to 18.3 micrograms/ml after oral administration of 250- to 1,000-mg doses. The regression analysis of Cmax on cefprozil dose showed a dose-linear response. The mean Cmax of cefaclor ranged from 15.2 to 16.7 micrograms/ml and did not change significantly on multiple dosing. The overall mean terminal half-life of cefprozil was 1.2 h and was invariant with respect to dose or duration of dosing. The area under the plasma-concentration-versus-time curve from 0 h to infinity (AUC0-infinity) of cefprozil increased in a dose-proportional manner with an increase in dose. The overall urinary recovery (61% of dose) and renal clearance values of cefprozil were generally invariant with respect to dose and duration of dosing. While cefprozil was apparently absorbed less rapidly and achieved lower Cmax values than cefaclor, the AUC0-infinity of cefprozil was nearly twofold greater than that of cefaclor. The half-life of cefprozil was also twofold longer than that observed for cefaclor. Although the urinary recovery of cefaclor (75% of dose) was significantly higher than that of cefprozil (61% of dose), the concentrations of cefprozil in urine remained significantly higher than those of cefaclor from 2 to 8 h postdosing. If the therapeutic concept is maintained that levels of beta-lactam antibiotics in plasma should exceed the MIC for the offending organisms over a period that approximates the dosing interval, then cefprozil would appear to be suitable for twice-daily administration, whereas cefaclor should probably be administered three or even four times a day.

Adult↗

PubMed1990

Comparison of cefprozil and cefaclor pharmacokinetics and tissue penetration.

The pharmacokinetics and tissue penetration, as judged by skin blister fluid, of cefprozil and cefaclor were examined in 12 healthy male volunteers. Doses of 250 and 500 mg of each drug were given to fasting subjects in a crossover fashion. Serially obtained plasma, skin blister fluid, and urine samples were analyzed for cefprozil or cefaclor by validated high-pressure liquid chromatographic methods. After oral administration of 250 and 500 mg of cefprozil, mean concentrations in plasma rose to peak levels (Cmax) of 6.1 and 11.2 micrograms/ml, respectively, and those of cefaclor were 10.6 and 17.3 micrograms/ml, respectively. The elimination half-life of cefprozil (1.3 h) was significantly longer than that of cefaclor (0.6 h), and as a result, the area under the curve for cefprozil was about two times greater than that for cefaclor. Both cephalosporins were primarily excreted unchanged in urine. The mean skin blister Cmax values were 3.0 and 5.8 micrograms/ml for cefprozil and 3.6 and 6.5 micrograms/ml for cefaclor after the 250- and 500-mg oral doses, respectively. The mean Cmax values in skin blister fluid for both cephalosporins were comparable and were significantly lower than the corresponding Cmax values in plasma. However, the levels of cefprozil and cefaclor in skin blister fluid declined more slowly than they did in plasma. The skin blister fluid half-life estimates for cefprozil were significantly longer than they were for cefaclor. Parallel to the observation in plasma, the mean skin blister fluid areas under the curve for cefprozil were significantly higher than they were for cefaclor. The plasma and skin blister fluid pharmacokinetic analyses suggest that the exposure of humans to cefprozil is significantly greater than that to cefaclor at the same dose.

Administration, Oral↗

PubMed1990

Comparison of the effects of food on the pharmacokinetics of cefprozil and cefaclor.

The objective of this study was to assess the effects of food on the pharmacokinetics of cefprozil and cefaclor. A group of 12 healthy male volunteers received a single 250-mg dose of cefprozil or cefaclor under fasting conditions as well as after the intake of food. There was a 1-week washout period between each treatment. Serial blood samples were collected and assayed for cefprozil or cefaclor by specific high-pressure liquid chromatographic methods. The mean +/- standard deviation peak concentration (Cmax) of cefprozil in plasma was 6.13 +/- 1.22 micrograms/ml under the fasting condition and 5.27 +/- 1.06 micrograms/ml after breakfast, and these values were not significantly different from each other. The corresponding median time to reach Cmax was prolonged after food intake, but this difference was not significant. The mean Cmax values of cefaclor decreased significantly from 8.70 +/- 2.72 micrograms/ml under the fasting condition to 4.29 +/- 1.52 micrograms/ml after breakfast, and the corresponding median times to reach Cmax were significantly prolonged. The mean half-lives of cefprozil and cefaclor were nearly identical for the two treatments, suggesting that the elimination kinetics of these cephalosporins remained unaltered when the drugs were administered with food. The area under the plasma-concentration-versus-time curves for fasted and fed conditions were not significantly different for both drugs. The results of this study indicate that the extent of absorption and rate of elimination of both cephalosporins remain unaltered in the presence of food. However, the absorption rate of cefaclor is significantly reduced in the presence of food, while that of cefprozil remains unaltered. As a result, the Cmax of cefaclor is significantly reduced in the presence of food, whereas that of cefprozil is not significantly affected. Cefprozil can be administered with a meal without markedly affecting levels in blood.

Adult↗