Pharmacokinetics of Phosphonomycin in Man I:Intravenous Administration

Kwan, K.C.; Wadke, D.A.; Foltz, Elwood L.

doi:10.1002/jps.2600600504

Cited by 32 publications

(24 citation statements)

References 14 publications

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“…Morphology of leukocytes and erythrocytes was normal on all occasions, as were platelets and VOL. 6,1974 on Notwithstanding the superior activity of cephalothin against gram-positive cocci, it should be noted that 63 out of the 65 strains of staphylococci and s-hemolytic streptococci tested were inhibited by 5 j.g of cefoxitin per ml, a concentration which is well within the therapeutically attainable range. With respect to the fecal-type streptococci, however, it is clear that neither antibiotic would be expected to be effective for systemic infections.…”

Section: Resultsmentioning

confidence: 99%

“…k,I was the first-order rate constant for overall elimination from the first compartment, whereas V1 was the apparent volume of this compartment. The above parameters were estimated by using the methods recommended by Wagner (11) and were refined on the basis of how well serum data predicted urinary excretion (6). For the intramuscular doses, V, and kei were calculated by using a pharmacokinetic modification of the modelindependent method of Kwan and Till (5).…”

Section: Methodsmentioning

confidence: 99%

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Cefoxitin and Cephalothin: Antimicrobial Activity, Human Pharmacokinetics, and Toxicology

Brumfitt

Kosmidis

Hamilton‐Miller

et al. 1974

Antimicrob Agents Chemother

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Cefoxitin, a semisynthetic cephamycin, has been compared with the widely used parenteral cephalosporin, cephalothin, in terms of antibacterial activity, human pharmacokinetics, and toxicity. For both compounds, minimal inhibitory concentrations were within the therapeutic range against the 156 gram-positive cocci tested (except group D streptococci), but cephalothin was 8 to 20 times more active. Regarding the 313 gram-negative organisms tested, both antibiotics were of approximately equal activity against cephalothin-susceptible strains, but cefoxitin was outstandingly superior against Providencia spp. and indoleproducing Proteus spp., and markedly better against Serratia marcescens and Bacteroides fragilis. Against these organisms, cefoxitin but not cephalothin would be expected to be therapeutically valuable. Antibiotic activity levels in the serum and urine of 18 human volunteers after parenteral administration were higher and more prolonged in the case of cefoxitin, which had an average terminal serum half-life of about 45 min and a urinary recovery of about 90%. Cefoxitin was entirely nontoxic and, given intramuscularly, slightly less painful then cephalothin. These preliminary results suggest that cephamycins may prove to be a significant chemotherapeutic advance.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Cefoxitin and Cephalothin: Antimicrobial Activity, Human Pharmacokinetics, and Toxicology

Brumfitt

Kosmidis

Hamilton‐Miller

et al. 1974

Antimicrob Agents Chemother

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“…Although pharmacokinetic properties of fosfomycin have been studied in humans (1,12) after intravenous and oral administration of 250-or 500-mg doses, the pharmacokinetics of larger doses employed therapeutically have not been investigated.…”

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confidence: 99%

Fosfomycin kinetics after intravenous and oral administration to human volunteers

Goto¹,

Sugiyama²,

Nakajima³

et al. 1981

Antimicrob Agents Chemother

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The pharmacokinetics of fosfomycin, administered intravenously and orally at two different doses (20 and 40 mg/kg of body weight), was studied in seven volunteers. The elimination profile of this antibiotic, when administered intravenously, followed a two-compartment kinetic model, independent of dosage, giving an elimination half-life of 2.23 ± 0.62 h and an average total volume of distribution at steady state of 0.34 liter/kg. Peak serum levels after rapid intravenous administration of 20 and 40 mg/kg were 132.1 ± 31.8 and 259.3 ± 32.5 ,ug/ml, respectively.Peak serum levels after oral administration were 7.1 ± 1.6 and 9.4 ± 3.6 ,ug/ml for the 20 and 40 mg/kg doses, respectively. During the first 24 h after administration, an average of 80% of the intravenous doses and less than 25% of the oral doses were recovered in the urine.Fosfomycin, a broad-spectrum bactericidal agent which inhibits the cell wall synthesis of both gram-positive and gram-negative bacteria (4,8,17), was discovered in Streptomyces fradiae fernentation broths (15).Although pharmacokinetic properties of fosfomycin have been studied in humans (1, 12) after intravenous and oral administration of 250-or 500-mg doses, the pharmacokinetics of larger doses employed therapeutically have not been investigated.The work reported here was undertaken specifically (i) to describe the pharnacokinetics of single relatively larger intravenous and oral doses of fosfomycin and (ii) to utilize these pharmacokinetic data to determine patient dosage schedules and methods of administration. MATERIALS AND METHODSHuman volunteers. Seven adult male volunteers participated in this study after informed written consent had been obtained. Their ages ranged from 25 to 56 years (mean ± standard deviation, 36.3 ± 12.3 years), and their body weight ranged from 45 to 70 kg (57.9 ± 7.0 kg). Prestudy physical examination and pre-and postdrug laboratory findings were normal. No volunteer had a history of allergy to antibiotics or other drugs. None had taken any drug during the month before the investigational period.Dosage. Fosfomycin disodium (lot CS-906; Meiji Seika Research Laboratories, Tokyo, Japan) dissolved in 0.9% saline was administered intravenously at a concentration of 100 mg/ml. Fosfomycin calcium salt (lot FOMDHT 2; Meiji Seika Research Laboratories) was administered orally.Experimental design. Each of the seven volunteers received fosfomycin disodium salt intravenously over 5 min at doses of 20 and 40 mg (potency) per kg. The same volunteers also received fosfomycin calcium salt orally at doses of 20 and 40 mg (potency) per kg. The oral dose was followed by the ingestion of 100 to 120 ml of water. Treatments were randomized and delivered in a crossover fashion, with 2-week intervals separating the respective doses. Subjects fasted overnight before each study; food was also withheld for 2 h after dosage. Blood samples (5 ml each) were drawn from an arm vein at 0 (1 min after the completion of injection), 0.25, 0.5, 1, 2, 4, 6, and 8 h after intravenous administrati...

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“…Since in the case of patients with renal insufficiency 80% of the elimi nation of the antibiotic is by glomerular filtration [10], the dose requires adjusting to the degree of renal insufficiency; the creatinin clearance test is a good index of the degree of renal insufficiency. Account should be taken of the extension of the half-life of the antibiotic to 12 h in the case of severe renal insufficiency.…”

Section: Discussionmentioning

confidence: 99%

Fosfomycin in Treatment of Chronic Urinary Tract Infection

et al. 1975

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A study was made of fosfomycin in the treatment of chronic urinary infection in 51 patients. 72% of the 67 bacteria isolated and tested in the laboratory with discs containing 50 μg of fosfomycin were found to be sensitive to the antibiotic. The majority of E. coli, Klebsiella, P. mirabilIs and Ps. aeruginosa strains were sensitive to the antibiotic. Generally, 60 mg of fosfomycin/kg body weight was administered intramuscularly, 6-hourly for 7–15 days. A clinical and bacteriological cure was obtained in 39 patients (76%), and after 4–6 weeks in 31 patients (61%). Blood and urine fosfomycin levels were determined in seven patients, three with normal renal function, three with moderate renal insufficiency, and one with severe renal insufficiency. The antibiotic levels and elimination time maintained a clear relation with the degree of renal insufficiency.

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Pharmacokinetics of Phosphonomycin in Man I:Intravenous Administration

Cited by 32 publications

References 14 publications

Cefoxitin and Cephalothin: Antimicrobial Activity, Human Pharmacokinetics, and Toxicology

Cefoxitin and Cephalothin: Antimicrobial Activity, Human Pharmacokinetics, and Toxicology

Fosfomycin kinetics after intravenous and oral administration to human volunteers

Fosfomycin in Treatment of Chronic Urinary Tract Infection

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