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M Pfeffer

Publications and source records attributed to M Pfeffer.

At least 109 records · Page 6Linked to original sources
PubMed1982

Pharmacokinetics of ceforanide.

The pharmacokinetic of ceforanide, a new parenteral cephalosporin antibiotic, were examined at intravenous and intramuscular doses of 250, 500, and 1,000 mg in healthy male volunteers. Over the above dosing range, ceforanide pharmacokinetics were essentially linear, with plasma clearances varying from 2.2 to 2.5 liters/h. The best present overall estimate of the drug's half-life was 2.9 h. Intramuscular ceforanide was 100% bioavailable, Peak intravenous serum levels were 39, 71, and 135 micrograms/ml at the end of 30-min infusions of 250, 500, and 1,000 mg; after intramuscular injections of 250, 500, and 1,000 mg, the respective peak serum levels were 21, 38, and 69 micrograms/ml. From 80 to 85% of the above doses were eliminated as unchanged.

Biological Availability↗
PubMed1981

Effect of dosing volume on intramuscular absorption rate of aminoglycosides.

The Loo-Riegelman method was applied to serum amikacin level data after intravenous and intramuscular administration. Intramuscular amikacin absorption can be described by first-order kinetics, but the absorption rate constant decreased from 1.95 hr-1 at a 125-mg dose to 1.00 hr-1 at a 750-mg dose. This rate change apparently is a physical phenomenon due to differing dosing volumes at different doses and attendant changes in the surface area to volume ratio at the injection site. Amikacin absorption rates on intramuscular injection can be maximized by giving several smaller injections rather than a single larger injection. This phenomenon should be generally observed with aminoglycoside antibiotics and could be partly responsible for reported variations in the absorption rate and the poor predictability of serum concentrations.

Absorption↗
PubMed1981

Ceforanide kinetics in renal insufficiency.

Ceforanide (500 mg) was infused intravenously over 30 min into six normal subjects, 10 nondialysis patients with renal insufficiency, and six hemodialysis patients. Dialysis patients received two ceforanide infusions, one immediately before dialysis and another during an interdialysis period. Sequential plasma samples over 24 to 72 hr were assayed for ceforanide. Peak ceforanide levels (mean = 69 +/- 12 micrograms/ml) and volumes of distribution did not vary with creatinine clearance (Clcr, ml/min/1.73 m2) and both plasma clearance and renal clearance decreased linearly as Clcr decreased. Mean nonrenal clearance (4.6 +/- 1.8 ml/min/1.73 m2) did not vary with Clcr. Mean half-life was 3 hr in the normal subjects, increasing to approximately 25 hr in patients with severe renal insufficiency. Hemodialysis resulted in a removal of approximately 21% of the dose of ceforanide. Dosing recommendations for patients with renal insufficiency are provided.

Adult↗
PubMed1981

Human pharmacokinetics and disposition of sarmoxicillin, a lipophilic amoxicillin prodrug.

Sarmoxicillin, an amoxicillin prodrug, is the methoxymethyl ester of hetamoxicillin. Esterification converted amoxicillin from an amphoteric to a cationic compound and resulted in a 30- to 600-fold increase in lipid partitioning. Oral absorption studies in normal subjects demonstrated that sarmoxicillin was only partially hydrolyzed by nonenzymatic and gut or hepatic first-pass metabolism and that significant quantities of intact ester appeared in the systemic circulation. Sarmoxicillin was converted to amoxicillin in plasma by hydrolysis of the acetone penicinate and the methoxymethyl ester bonds. Significant amoxicillin levels were demonstrated in saliva after administration of sarmoxicillin, but not amoxicillin, over a 250- to 1,000-mg dose range. Differences in the absorption, distribution, or metabolism of amoxicillin were also evident in the lower plasma amoxicillin maximum concentration and area under the curve and longer half-life after sarmoxicillin administration. Differences in the distribution of this lipophilic ester could result in a significant increase in tissue penetration and subsequent therapeutic efficacy of amoxicillin when administered as sarmoxicillin.

Amoxicillin↗
PubMed1980

Human pharmacokinetics of a new braod-spectrum parenteral cephalosporin antibiotic, ceforanide.

The pharmacokinetics of the l-lysine salt of ceforanide were studied after intravenous administration of 1132 and 2264 mg as 30-min constant-rate infusions and after intramuscular administration of 556 and 1132 mg. The peak intravenous plasma concentrations were 136 and 222 microgram/ml at termination of infusion, and 12-hr trough concentrations were 5.9 and 9.0 microgram/ml, respectively. The peak intramuscular plasma concentrations were 38 and 74 microgram/ml at 1.0-1.3 hr after dosing, and 12-hr trough concentrations were 3.9 and 6.7 microgram/ml, respectively. When 19 successive intravenous and intramuscular doses at these levels were administered at 12-hr intervals, there was no tendency toward drug accumulation. The major drug elimination route was urinary excretion; 85% of the dose was excreted unchanged in the urine within 12 hr, and no metabolites with antibiotic activity were observed in urine. The mean terminal plasma half-life was 2.98 hr, the mean plasma protein binding was 80.6%, the steady-state volume of distribution was 12 liters, the plasma clearance was 45.9 ml/min/1.73 m2, and the renal clearance was 34.9 ml/min/1.73 m2. The pharmacokinetic properties and antibacterial activity spectrum indicate that this antibiotic should be effective in treating human bacterial infections when administered at 12-hr intervals. It is presently under clinical investigation.

Adult↗
PubMed1980

Pharmacokinetics of subcutaneous and intramuscular butorphanol in dogs.

Butorphanol tartrate was administered intramuscularly and subcutaneously to adult male and female dogs at a dose of 0.25 mg/kg. No significant absorption lag time and no significant difference bwtween peak intramuscular and subcutaneous serum concentrations were observed. The mean peak serum concentration was 29 ng/ml at mean times of 28 min after subcutaneous administration and 40 min after intramuscular administration. There were no significant differences in the pharmacokinetics of butorphanol in dogs with either route. The serum half-life was 1.62 hr, and the serum clearance was 3.45 liters/kg/hr. The apparent volume of distribution of butorphanol was 7.96 liters/kg. Although considerable inter- and intraanimal variation in Cmax and AUC was observed, there was no significant difference in the area under the serum concentration versus time curves, and the two administration routes were considered bioequivalent.

Animals↗
PubMed1980

Comparative pharmacokinetics of ceforanide (BL-S786R) and cefazolin in laboratory animals and humans.

Ceforanide (BL-S786R) is a new, broad-spectrum, parenteral cephalosporin. Pharmacokinetic properties were determined in rats (100 mg/kg), rabbits (30 mg/kg), dogs (25 mg/kg), and humans (2 g or 30 mg/kg) and compared with equivalent single doses of cefazolin. Plasma half-lives for ceforanide and cefazolin were 1.1 and 0.5 h in the rat, 5 and 0.3 h in the rabbit, 1 and 0.8 h in the dog, and 2.6 and 2 h in humans, respectively. The slower elimination of ceforanide, as reflected by longer plasma half-life, larger area under the curve, and peak plasma concentrations, was due to slower body and renal clearances. The apparent volumes of distribution of ceforanide and cefazolin were comparable. Rats, dogs, and humans excreted 80 to 100% of the ceforanide dose in the 0- to 24-h urine; rabbits excreted only 50%. Tubular secretion constituted 50% of ceforanide renal excretion in rabbits, dogs, and humans and 90% in rats; the remainder was excreted by glomerular filtration. There was no apparent correlation between the extent of tubular secretion and degree of plasma protein binding in different species. There was no significant pharmacokinetic interaction between ceforanide and amikacin in the rat. The slower elimination kinetics of ceforanide are indicative of the potential for a longer dosing interval and more effective antibiotic therapy as compared with available cephalosporins.

Adult↗
PubMed1979

Clinical pharmacokinetics and safety of high doses of ceforanide (BL-S786R) and cefazolin.

The pharmacokinetics and safety of ceforanide and cefazolin were compared in normal subjects after 30-min intravenous infusions of 2-, 3-, and 4-g single doses and 4-g twice-daily doses for 10 days. No significant differences were observed in plasma-renal pharmacokinetic parameters between single and multiple doses of ceforanide. Half-life (t((1/2)), 2.8 h), plasma clearance (Cl(p), 48 ml/min per 1.73 m(2)), and renal clearance (Cl(0-12h) (r), 47 ml/min per 1.73 m(2); tubular secretion, 44%, and glomerular filtration, 56%) did not change with increased dose or on multiple dosing. No significant change was observed in t((1/2)) (1.9 h), area under the plasma concentration-time curve, Cl(r) (60 ml/min per 1.73 m(2); tubular secretion, 80%, and glomerular filtration, 20%), or Cl(p) (75 ml/min per 1.73 m(2)) for 4-g single doses compared with twice-daily administration of cefazolin. A small increase in cefazolin clearance was observed when plasma concentrations were greater than 100 mug/ml, when the single dose was increased from 2 to 4 g; this was a result of the decrease in percentage of plasma protein binding and increased renal clearance due to increased glomerular filtration. The increase in renal clearance resulted in a lack of linear proportionality of the plasma area under the curve with dose over a range of 2 to 4 for both cephalosporins, although this effect was much less marked with ceforanide. Both compounds were well tolerated both locally and systemically. There was no evidence of any change in renal function based on clearances of drug, p-aminohippuric acid, or creatinine, and other standard clinical parameters.

Adult↗
PubMed1977

Comparative human oral clinical pharmacology of cefadroxil, cephalexin, and cephradine.

At equivalent oral doses, cefadroxil has a longer serum half-life, slower urinary excretion rate, greater area under the serum level versus time curve than cephalexin or cephradine, and peak serum concentrations that are 75 to 80% those of cephalexin. The calculated, apparent in vivo volume of distribution of cefadroxil is greater than that of cephalexin. These properties infer greater persistence of cefadroxil in serum and urine and more prolonged in vivo bacterial exposure to cefadroxil than to cephalexin or cephradine. Neither cefadroxil nor cephalexin demonstrates drug accumulation on repeated administration. The serum levels achieved by cefadroxil are unaffected by food. The pharmacokinetic properties of cefadroxil are supportive of the development of clinical efficacy data which could indicate that cefadroxil could be administered at 12-h intervals.

Adult↗