Louise J. Riff

Vancomycin pharmacokinetics in patients with various degrees of renal function.

The influence of age, protein binding, and renal function on the pharmacokinetics of intravenous vancomycin was evaluated in 37 adult patients with various degrees of renal function. Patients were categorized into three groups based on measured creatinine clearance (CLCR): groups 1, 2, and 3 had 24-h CLCRs of greater than 70, 40 to 70, and 10 to 39 ml/min per 1.73 m2, respectively. After 1 h of intravenous infusion, concentrations of vancomycin in serum declined in a biexponential manner in all patients. Diminished renal function in groups 2 and 3 was accompanied by a lower total body vancomycin clearance (CL) (52.6 and 31.3, respectively, versus 98.4 ml/min per 1.73 m2) and a lower renal vancomycin clearance (CLR) (48.2 and 19.8, respectively, versus 88.0 ml/min per 1.73 m2) than in group 1. No significant differences in apparent distribution volume of the central compartment or apparent distribution volume at steady state were observed. Mean serum protein binding of vancomycin was 30% and was not significantly affected by renal function. Stepwise multiple linear regression analysis revealed that CLCR was the strongest predictor of vancomycin CL (r = 0.77, P less than 0.001) and vancomycin CLR (r = 0.87, P less than 0.001). Age did not significantly improve these correlations once CLCR was included. The relationship of vancomycin CL and CLCR was utilized to develop the following equation to dose vancomycin in the majority of renally impaired patients: dose (milligrams per kilogram per 24 h) = 0.227CLCR + 5.67, where CLCR is standardized to milliliters per minute per 70 kg. The practical dosing intervals that the calculated dose can be divided into and administered include 8, 12, 24, and 48 h based on the CLCR of the patient.

SUSCEPTIBILITY AND IMMUNITY TO COMMON UPPER RESPIRATORY VIRAL INFECTIONS—THE COMMON COLD

Excerpt Common upper respiratory viral infections, despite their frequency, have been something of an enigma to physicians and scientists in general. Little has been known about their specific etio...

Netilmicin and Gentamicin: Comparative Pharmacology in Humans

Thirteen male subjects received 1 mg of either gentamicin or netilmicin per kg, first intramuscularly and then intravenously. After the intramuscular dose, concentrations of gentamicin in the serum were more variable than those of netilmicin. After the intravenous dose, the distribution phase of netilmicin was twice as rapid as gentamicin. The average half-times of the elimination phase were similar, but there was marked variability among the subjects receiving gentamicin. Serum clearance of netilmicin was more rapid than that of gentamicin and could not be attributed to renal elimination. The data indicate that, after intramuscular administration, netilmicin may produce more predictable blood levels than gentamicin and suggest that the body distribution of netilmicin may differ from that of gentamicin.

Simulation of Vancomycin Peak and Trough Concentrations Using Five Dosing Methods in 37 Patients

Five methods of dosing vancomycin (Matzke, Moellering, Nielsen, Lake‐Peterson, and manufacturers) were simulated in 37 patients. Ten serum samples were obtained after a 1–hour intravenous infusion of 6.2–20 mg/kg total body weight. A preinfusion serum sample was obtained from patients not studied on the first dose. Initial estimates of pharmacokinetic values were made using nonlinear iterative least squares regression and serum concentration‐time data. These data were fitted to a two‐compartment, open‐infusion model. Simulations of the peak and trough serum concentrations at steady state for each patient were determined by multiple‐dose simulated pharmacokinetics and each patients pharmacokinetic values using the regimen suggested by each of the five methods. Steady‐state serum concentrations, predicted systemic clearance by each method (except Lake‐Peterson), and the daily dose for each patient recommended by each method were determined. All the methods underpredicted actual drug clearance, with the Nielsen method having the lowest prediction. The Matzke method recommended the largest dosage. Using each of the methods, only 3–16% of patients would have achieved recommended peak and trough serum concentrations. In the simulation model used, no method performed satisfactorily in attaining the desired vancomycin peak and trough concentrations. We suggest that the Lake‐Peterson method could be used initially, provided that monitoring is also performed to adjust the dosage regimen further.

Association Between the Erythrocyte Hemagglutination Inhibitor and the M-N Blood Group Substances.

Summary The data reported indicate that a stromal glycoprotein, homogeneous by several criteria, is an active inhibitor of viral hemagglutination and has M-N blood group specificity. Both properties decrease in activity when the protein is removed from solution by mixing with influenza virus and centrifuging the mixture or when it is reacted with anti-M-N serum. It has always been observed that the disappearance of the one property of the protein is accompanied by the disappearance of the other. These results are interpreted as an indication that a single protein possesses both of these properties.

Double-Blind Comparison of Cephacetrile with Cephalothin/Cephaloridine

Under double-blind protocol, a controlled comparison was made between a new cephalosporin, cephacetrile, and cephalothin or cephaloridine. The patients primary physician determined the indications for treatment, and the dosage was uniform for each route of administration. Infecting strains of staphylococci and Proteus mirabilis had a lower median inhibitory concentration for cephalothin than cephacetrile; the opposite was true for Escherichia coli and Klebsiella species. The average peak serum level 1 h after a dose of 2 g intravenously was 74.9 ± 21 and 21.5 ± 8.7 μg/ml for cephacetrile and cephalothin, respectively; 6 h after the dose, the respective levels were 12.4 ± 4.3 and 3.7 ± 0.9 μg/ml. Renal clearances were similar and the plasma clearance was proportional to the serum levels. In the urine, the concentration of cephacetrile was three times higher than that of cephalothin. Based on a percentage of therapeutic potential, success in the treatment of infections with susceptible organisms was 42 and 44% for the two different drug regimens. Initial bacterial resistance was found in about one-fifth of infections, and concomitant therapy with other drugs was practiced in one-half of the treatment courses. Intravenous use of cephacetrile was discontinued prematurely more often than was use of cephalothin, suggesting less tolerance. Although there was no overt toxicity, more than 75% of patients on either regimen had some form of unwanted response to treatment, the most common being superinfection. From this limited but controlled experience, cephacetrile can be considered comparable to cephalothin in antimicrobial treatment and overall side reactions.