Pharmacokinetics of Minocycline in Renal Failure

Welling, Peter G.; Shaw, W. R.; Uman, Stephen J.; Tse, Francis L. S.; Craig, William A.

doi:10.1128/aac.8.5.532

Cited by 47 publications

(45 citation statements)

References 10 publications

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“…A close comparison between murine and human pharmacokinetics is not feasible from the available data. However, minocycHne serum concentrations associated with full protection of the mice were in the range of serum concentrations achievable in humans where peak levels have been found at 8-75 mg/1 after a single iv infusion of 100 mg of minocycHne (Welling et al, 1975). Pyrimethamine at 8-5 mg/kg did not enhance significantly the cure rate obtained with 100 mg/kg per day of minocycHne.…”

Section: Discussionmentioning

confidence: 91%

Activity of minocycline against Toxoplasma gondii infection in mice

Chang

Comte

Piguet

et al. 1991

J Antimicrob Chemother

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The chemotherapeutic activity of minocycline, a semi-synthetic tetracycline analogue, was evaluated in a murine model of toxoplasmosis. A lethal acute toxoplasmosis was produced by injecting 10 5 tachyzoites of the RH strain of Toxoplasma gondii into the peritoneal cavities of Swiss-Webster mice. When infected mice were treated once daily for 12 days, starting 2 h after challenge, the survival and cure rates were 100% and 40% respectively after minocycline alone (100 mg/kg per day), 0% and 0% after pyrimethamine alone (8-5 mg/kg per day), and 100% and 50% after combination of the two drugs at the same dosages. Absolute survival and cure with minocycline were observed when mice were treated with two daily doses of 100 mg/kg for 12 days. Mice chronically infected with a low virulent strain of T. gondii (Me49) showed a significant reduction in the number of brain cysts after three weeks of treatment with 50 mg/kg per day of minocycline. Minocycline serum levels after a single oral administration of 50 mg/kg or 100 mg/kg to normal mice, peaked at 1-8 mg/1 and 10 mg/1 after 1 h, respectively, and showed an extended half-life.

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Section: Discussionmentioning

confidence: 91%

Activity of minocycline against Toxoplasma gondii infection in mice

Chang

Comte

Piguet

et al. 1991

J Antimicrob Chemother

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“…(1) The complex rate constants a and /3 are given by equation 2, where k12 and k2l are first-order rate constants for drug distribution from the central to the tissue compartment and from the tissue to the central compartment, respectively, kei is the firstorder rate constant for drug elimination from the central compartment, a > /3, and the elimination half-life of netilmicin in serum is given by 0.693//3. a = 0.5 [(kl2 + k2l + kel) ± ](k12 + k2l + ke1)2 -4ki2kke] (2) Individual serum levels were fitted to equation 1 using the digital computer program NREG (15).…”

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confidence: 99%

Netilmicin Pharmacokinetics After Single Intravenous Doses to Elderly Male Patients

Welling

Baumueller

Lau

et al. 1977

Antimicrob Agents Chemother

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The pharmacokinetics of the new aminoglycoside antibiotic netilmicin were examined after single intravenous injections at two different dose levels to elderly male patients. The drug obeyed two-compartment model kinetics in serum, and elimination was monoexponential from 1 to 2 h after dosing. Netilmicin levels in serum were above minimum inhibitory concentration values for most susceptible organisms for up to 8 h after dosing in normal individuals and for at least 12 h in uremic patients. Urine levels of netilmicin were uniformly above minimum inhibitory concentration values throughout 24 h after dosing. Netilmicin distribution characteristics were largely independent of both dose level and renal function. Netilmicin elimination kinetics were independent of dose level but were markedly influenced by renal function. Relationships are described between netilmicin elimination and renal function indicators, which provide a basis for dosage adjustment in individuals with renal function impairment.Netilmicin, the 1-N-ethyl derivative of sisomicin, is a new aminoglycoside which is effective against gram-negative bacteria, including strains resistant to gentamicin, sisomicin, and tobramycin (5,6,9).In a previous study at this institution, netilmicin was shown to be clinically effective and free from toxic side effects when given intramuscularly to elderly male patients at doses of 1.0 to 2.5 mg/kg every 8 h for 7 days (A. Baumueller and P. 0. Madsen, submitted for publication). A preliminary study in a similar patient population showed that after rapid intravenous irjection, netilmicin had a serum halflife of about 4.5 h, and the half-life was linearly related to serum creatinine (Baumueller and Madsen, submitted for publication).Here we report on the pharmacokinetics of netilmicin after single intravenous doses to elderly male patients with normal and impaired renal function. MATERIALS AND METHODSSubjects and protocols. Subjects were 42 patients in the urology ward of the Veterans Administration Hospital, Madison, Wis. Details of subjects' ages, weights, creatinine clearances, and serum creatinine values are described in Table 1. Almost all of the patients were suffering from lower urinary tract obstruction, infections associated with lower urinary tract obstruction, urethral stricture, carcinoma or hyperplasia of the prostate, or bladder tumor. Some patients had indwelling bladder catheters; most of them were not bedridden during the study.For analysis, patients were divided into three groups based on creatinine clearances. Groups 1, 2 and 3 had creatinine clearances greater than 100 ml/ min, between 50 and 100 ml/min, and less than 50 ml/min, respectively. Creatinine clearances were obtained from 12-h urine collections, except in the case of some severely uremic patients where 24-h urine clearances were obtained. Patients received netilmicin by rapid intravenous injection into a forearm vein at dose levels of 1 or 2 mg/kg. The injection was administered in 5 ml of physiological saline, and the injection time was 2 m...

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“…The influence of renal disease on the elimination of the tetracycline derivate minocycline (MC = 7-dimethylamino-6-deoxy-6-methyl-tetracycline) has been investigated experimentally by several authors in recent years [4,11,13,18]. In our own experiments [14] we found that the elimination rate of the antibiotic is practically independent of kidney function because even in anuric patients the elimination was only about 15% slower than normal.…”

Section: Introductionmentioning

confidence: 94%

One-dose and multiple-dose kinetics of minocycline in patients with renal disease

1977

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Kinetic analysis of minocycline concentrations in plasma and urine resulted in the following findings: In normal subjects the biological half-life is about 17 hours after the first dose and 21 hours after repeated administration. The renal drug clearance is only about 8% of the overall plasma clearance which is independent of renal function with a mean value of 47 ml/min. The fraction of the absorbed dose eliminated unchanged in the urine is only 9--19%. As a consequence the elimination rate of the drug is practically independent of renal function and decreases only 9--19% in anuric patients. The renal drug clearance depends linearly on renal function. The gastro-intestinal bio-availability of minocycline from the coated tablet preparation is incomplete. The cumulative behaviour of the drug corresponds to the kinetic parameters determined after repeated administration. It is suggested that the usual dosage regimen should be used in patients with renal disease.

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Pharmacokinetics of Minocycline in Renal Failure

Cited by 47 publications

References 10 publications

Activity of minocycline against Toxoplasma gondii infection in mice

Activity of minocycline against Toxoplasma gondii infection in mice

Netilmicin Pharmacokinetics After Single Intravenous Doses to Elderly Male Patients

One-dose and multiple-dose kinetics of minocycline in patients with renal disease

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