Biomedical subjects

W C Shyu

Publications and source records attributed to W C Shyu.

At least 73 records · Page 4Linked to original sources

PubMed1993

Penetration of cefprozil into tonsillar and adenoidal tissues.

Penetration of cefprozil into tonsillar and/or adenoidal tissues was investigated for patients undergoing tonsillectomy and/or adenoidectomy. A total of 29 patients ranging in age from 2 to 14 years participated in the study. The tonsils and/or the adenoids were removed at times ranging from 0.33 to 3.17 h after oral administration of a dose of either 7.5 or 20 mg/kg of body weight. A blood sample was also collected as soon as the tissue sample was removed. Plasma, tonsil, and adenoid samples were analyzed for cis and trans isomers of cefprozil by high-performance liquid chromatographic assays. The concentrations of the cis isomer of cefprozil in plasma ranged from 0.60 to 9.87 micrograms/ml at the 7.5-mg/kg dose level and from 1.04 to 20.40 micrograms/ml at the 20-mg/kg dose level. The corresponding concentrations of the cis isomer in tonsil tissue ranged from 0.48 to 2.42 micrograms/g and from 1.00 to 4.29 micrograms/g, respectively. The corresponding concentrations of the cis isomer in adenoid tissue ranged from 0.40 to 4.20 micrograms/g and from 1.74 to 4.94 micrograms/g, respectively. The concentrations of the trans isomer were about 1/10 of those observed for the cis isomer. The median ratios of the cefprozil concentration in tonsillar tissue to that in plasma were 0.37 and 0.47 for patients receiving a 7.5- or a 20-mg/kg oral dose of cefprozil, respectively. The corresponding median ratios for the adenoidal tissue were 0.46 and 0.82, respectively. The cefprozil concentrations in either the tonsillar or the adenoidal tissue at both dose levels over 3.17 h after dosing are much higher than the MICs for common pathogens which cause pharyngitis or tonsillitis.

Adenoidectomy↗

PubMed1993

Compressive radial nerve palsy induced by military shooting training: clinical and electrophysiological study.

Ten recruited soldiers developed acute left wrist drop and numbness on the back of the thumb after a three hour military shooting training. Neurological examination disclosed decreased muscle power (0-2/5) of left wrist dorsiflexion, hypalgesia and hypaesthesia on the radial side of the left hand, and diminished brachioradialis reflex. Electrophysiological studies showed prolonged distal latency, reduced amplitude and slowness of left radial nerve motor conduction velocity between the axilla and elbow. Electromyography (EMG) revealed fibrillation potentials at rest, polyphasic motor unit and an incomplete interference pattern at volition over the extensor digitorum communis and brachioradialis. Nine patients recovered completely clinically and electrophysiologically between nine and 12 weeks after the onset of the palsy. Sensation recovered faster than the weakness. One patient failed to recover after three months, possibly because of the longer duration of nerve compression. Longer nerve compression time and sustained, decreased muscle power with signs of active denervation in EMG are indicators of poor prognosis.

Adult↗

PubMed1993

Effects of time of administration and posture on the pharmacokinetics of cefprozil.

The effects of time of administration, sleep and posture on the pharmacokinetics of cefprozil were evaluated in a single-dose 3-way crossover study. After a 6-hour fast, 12 healthy male volunteers received oral cefprozil 250mg at 1200h (treatment A), 1200h (treatment B) and 2400h (treatment C) with a 7-day washout interval between each treatment. During the study period, volunteers receiving treatment A remained in a sitting/standing position or were ambulatory, those receiving treatment B were in the supine position, and those receiving treatment C were sleeping. Blood samples were taken over an 8-hour period and the plasma samples were analysed for the concentrations of cefprozil by a high performance liquid chromatography-ultraviolet method. Plasma concentration vs time data were analysed using noncompartmental analysis methods. Mean peak plasma concentrations (Cmax) were 4.51, 5.02 and 4.91 mg/L for treatments A, B and C, respectively. Corresponding mean values of the area under the plasma concentration-time curve (AUC(0-infinity)) were 12.6, 12.6 and 14.2 mg/L.h, respectively. The mean half-life (t1/2) values were 1.30, 1.23 and 1.50 hours for treatments A, B and C, respectively. Mean AUC(0-infinity), Cmax and t1/2 values following treatment B were not significantly different from those of treatment A. However, the mean AUC(0-infinity) and t1/2 values of cefprozil following treatment C were significantly greater than those of either treatment A or B. The mean Cmax value following treatment C was not significantly different than that of either treatments A or B. From these results, it was concluded that posture has no effect on the pharmacokinetics of cefprozil.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Serum-ascites albumin concentration gradient and ascites fibronectin in the diagnosis of malignant ascites.

BACKGROUND: The differential diagnosis between malignant and nonmalignant ascites by using laboratory parameters has not been completely achieved so far. METHODS: The authors studied serum-ascites albumin concentration gradients ([albumin]s - [albumin]a), ascites fibronectin and various parameters in 149 consecutive patients with ascites (including Group 1: 22 patients with intraabdominal malignant lesions; Group 2: 81 patients with chronic liver disease; and Group 3: 46 patients with hepatocellular carcinoma [HCC]). RESULTS: The concentrations of fibronectin, albumin, protein, lactate dehydrogenase, and carcinoembryonic antigen in ascites were significantly higher in Group 1 than in Group 2 (P < 0.001). By contrast, the [albumin]s - [albumin]a was significantly lower in Group 1 than in Group 2 (P < 0.001). None of these parameters was useful in differentiating the ascites of chronic liver disease from that of HCC. In this study, to differentiate malignant ascites from the ascites caused by liver diseases, [albumin]s - [albumin]a (< 1.5 g/dl) and the fibronectin level in the ascites (> 100 micrograms/ml) provided diagnostic accuracy (96.8% and 95.9%, respectively) as precise as those of the levels of albumin (> 1.6 g/dl), protein (> 2.5 g/dl), and lactate dehydrogenase (> 60 U/l; 97.9%, 96.7%, and 94.8%, respectively) in ascites. These results were better than that of carcinoembryonic antigen level (> 1.5 ng/ml, 80.9%). CONCLUSIONS: The authors concluded that [albumin]s - [albumin]a offered the best method to survey malignant ascites because of its sensitivity (100%).

Albumins↗

PubMed1992

Oral absolute bioavailability and intravenous dose-proportionality of cefprozil in humans.

The absolute bioavailability (F) and dose proportionality of cefprozil were investigated in a parallel design study with an embedded two-way crossover leg. Twenty-four healthy male subjects divided into 3 dosing groups received a single 250-, 500-, or 1000-mg dose of cefprozil by a 30-minute intravenous infusion. Subjects assigned to the 500-mg dose group also received a 500-mg oral dose of cefprozil in crossover manner with a wash-out period of 7 days between each treatment. Cefprozil consists of cis and trans isomers in an approximate 90:10 ratio. Serial blood and urine samples were collected and analyzed for the concentrations of the cis and trans isomers of the cephalosporin using high-pressure liquid chromatographic assay with UV detection methods. After the 250-, 500-, and 1000-mg intravenous administration of cefprozil, the peak concentrations were 13.2, 26.0, and 48.5 micrograms/mL, and area under the plasma concentration versus time profiles were 17.2, 31.4, and 58.1 micrograms.hour/mL, respectively, for the cis isomer increasing in a dose proportional manner. Total body clearance, renal clearance, and volume of distribution at steady state, adjusted for body weight, were not significantly different among all groups. Mean residence time, elimination half-life, and urinary recovery were invariant with the dose. Based on the plasma and urine data, the estimates of F were 89% and 94% for the cis isomer, respectively. The plasma concentrations of the trans isomer were about 1/10th of the cis isomer, and all parameters were similar to those observed for the cis isomer. In summary, cefprozil exhibits linear pharmacokinetics and is essentially completely absorbed after oral administration.

Adult↗

PubMed1992

Absolute bioavailability of cefprozil after oral administration in beagles.

The absolute bioavailability of cefprozil, a new oral cephalosporin, in four beagles was evaluated. In this two-way crossover study, each dog received a 125-mg dose of cefprozil either as an oral aqueous solution or as a 15-min intravenous infusion. A high-performance liquid chromatographic assay with UV detection was employed for the determination of cefprozil concentrations in plasma and urine. Key pharmacokinetic parameters were calculated by noncompartmental methods. Cefprozil was well absorbed after oral administration, and peak concentrations of 17.6 to 26.6 micrograms/ml were attained at 60 min after drug administration. The apparent elimination half-life of cefprozil was about 70 min. The renal clearance was about 60% of total body clearance and is suggestive of significant nonrenal clearance. The absolute bioavailability of cefprozil ranged from 67.1 to 79.1% in the dogs.

Administration, Oral↗

PubMed1992

Excretion of cefprozil into human breast milk.

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 of cis and trans isomers in an approximately 90:10 ratio. Serial blood, urine, and breast milk samples were collected and analyzed for the concentrations of the cis and trans isomers by a specific high-pressure liquid chromatography-UV assay. The mean pharmacokinetic parameters for both isomers were essentially the same. The mean peak concentrations in plasma for the cis isomer were 14.8 micrograms/ml, and the area under the concentration curve was 54.8 micrograms.h/ml. The mean values of elimination half-life, renal clearance, and urinary excretion for the cis isomer were 1.69 h, 164 ml/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 micrograms/ml, with the maximum concentration appearing at 6 h after dosing. The average maximum concentration in milk of the trans isomer was less than 0.26 micrograms/ml. The concentrations of the trans 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 micrograms/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 cefprozil 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.

Administration, Oral↗

PubMed1992

Effect of antacid on the bioavailability of cefprozil.

The effect of antacid on the bioavailability of cefprozil was investigated in a two-way crossover study. Eight healthy male subjects received a single 500-mg oral dose of cefprozil with and without coadministration of 30 ml of an antacid suspension containing magnesium hydroxide and aluminum hydroxide (Maalox). Cefprozil consists of cis and trans isomers in an approximate 90:10 ratio. When cefprozil was administered alone (treatment A), the mean maximum concentrations (Cmax) of the cis and trans isomers were 9.2 and 1.2 micrograms/ml, respectively. When cefprozil was coadministered with Maalox (treatment B), the Cmax values of the cis and trans isomers were 8.7 and 1.3 micrograms/ml, respectively. The mean values of the area under the curve from time zero to infinity (AUC0-infinity) were 27.7 and 3.5 micrograms.h/ml for treatment A and 27.5 and 3.5 micrograms.h/ml for treatment B for the cis and trans isomers, respectively. The other pharmacokinetic parameters, time to Cmax, elimination half-life, mean residence time, renal clearance, and percent urinary excretion, were essentially the same for the two isomers. The respective values of the elimination half-life for the cis and trans isomers were 1.36 and 1.32 h for treatment A and 1.36 and 1.42 h for treatment B. Mean urinary excretion was 63 and 60% for treatment A and 58 and 56% for treatment B for the cis and trans isomers, respectively. No significant differences between the two treatments were found for any of the pharmacokinetic parameters for either isomer. For the cis isomer, bioavailability point estimates (90% confidence intervals) of the mean Cmax and AUG0-infinity values for the Maalox treatment relative to those for the reference treatment were 95% (87%, 103%) and 99% (95%, 104%), respectively. For the trans isomer, the value were 109% (92%, 126%) for Cmax and 97% (88%, 106%) for AUC0-infinity. On the basis of the results of this study, it is concluded that the bioavailability of cefprozil is not affected by the coadministration of Maalox.

Administration, Oral↗

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

Simultaneous high-performance liquid chromatographic analysis of cefprozil diastereomers in a pharmacokinetic study.

Cefprozil, a new oral cephalosporin, consists of a 90:10 cis:trans isomer mixture. Sensitive, specific and reproducible high performance liquid chromatographic methods have been developed for the simultaneous quantification of the two stereoisomers of cefprozil in plasma and urine samples from human and rats. Cephalexin acted as the internal standard. Plasma protein was precipitated with acetonitrile and trichloracetic acid with subsequent extraction of acetonitrile. After vortexing and centrifuging, the aqueous phase was injected onto a reverse phase C8 column. Urine samples were acidified with sodium acetate buffer (pH 3.8) and then directly injected onto a reverse phase C18 column. The detector was set at 280 nm. These methods were applied to determine protein binding of both isomers in human and rat sera, and to perform a pharmacokinetic study in human. Results showed that both isomers bound moderately to serum proteins with no interference by the other isomer. The pharmacokinetic study in human indicated that cefprozil was well absorbed and the cis and trans isomers have similar pharmacokinetics.

Animals↗

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

[Compressive radial nerve palsy induced by military shooting training--a case report].

A newly recruited soldier suffered a sudden onset of wrist-drop of left hand and numbness on the back of thumb after a military training course in target shooting. An examination disclosed decreased muscle power (0/5) in the left wrist dorsiflexion, disturbance of pain-temperature sensation on the radial side of left hand and absence of the deep tendon reflex of brachioradialis. Electrophysiological studies showed slowness of motor conduction velocity, delay of distal latency and reduced amplitude. EMG revealed fibrillation over the extensor digitorium communis (EDC) at rest, brachioradialis and prolongation of polyphasic MUAPs over EDC. Left radial nerve mononeuropathy induced by mechanical compression of the radial nerve on the spiral groove of humerus was conspicuous. We attempted to discuss the disease etiology, electrophysiological findings and treatment.

Adult↗

PubMed1990

DNA measurements in chronic hepatitis, cirrhosis and hepatocellular carcinoma.

It has been documented that chronic hepatitis may progress to cirrhosis and then develop hepatocellular carcinoma (HCC). To test whether abnormal cellular DNA increases along this line of development, liver tissues from 48 patients with chronic hepatitis, 17 with cirrhosis, and 8 with HCC were investigated for cellular DNA content with a scanning microdensitometer. Seven of 8 HCCs and 2 cirrhotic livers adjacent to HCC had abnormally increased cellular DNA content. Only 4 livers from patients with chronic liver diseases other than HCC had abnormal cellular DNA content. The cellular DNA content in livers not accompanying HCC was not related to the patient's age, histological diagnosis, and hepatitis inflammatory activity. The results confirmed the increase of cellular DNA content in HCC, but did not provide evidence of a progressively increasing DNA content from chronic hepatitis to liver cirrhosis. However, cirrhotic livers with abnormal hepatocytic DNA content deserve careful follow-up for the early detection of HCC.

Adult↗

PubMed1990

Pharmacokinetics of cefprozil in infants and children.

Twenty pediatric patients (ages, between 8 months and 8 years) received a single oral dose of cefprozil at levels of 15 and 30 mg/kg of body weight. Cefprozil consists of cis (BMY-28100) and trans (BMY-28167) isomers in an approximately 90:10 ratio. Six plasma samples were collected from each pediatric patient and assayed for drug concentrations. As measured by a microbiological assay, peak concentrations of 11.16 and 15.93 micrograms of cefprozil per ml occurred at 1 h for patients who received the 15- and 30-mg/kg doses, respectively. The respective mean half-lives of cefprozil were 1.77 and 2.14 h, and the respective mean areas under the curve were 28.05 and 45.28 micrograms.h/ml for patients who received the 15- and 30-mg/kg doses. When measured by a high-pressure liquid chromatography method, peak concentrations of 12.09 and 18.04 micrograms of the cis isomer per ml were obtained at 1 h, with mean half-lives of 1.63 and 2.06 h and mean areas under the curve of 30.48 and 49.34 micrograms.h/ml in patients who received the 15- and 30-mg/kg doses, respectively. For the trans isomer, peak concentrations of 1.16 and 1.63 micrograms/ml occurred at 1 h, respectively, with mean half-lives of 1.61 and 1.65 h and mean areas under the curve of 2.89 and 4.34 micrograms.h/ml in patients who received the 15- and 30-mg/kg doses, respectively.

Administration, Oral↗

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

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↗