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Biomedical subjects

W A Craig

Publications and source records attributed to W A Craig.

18 recordsLinked to original sources
PubMed1978

Pharmacokinetics of intravenous erythromycin.

Erythromycin pharmacokinetics were examined following intravenous infusion to male subjects. The biological half-life of erythromycin in serum was 2 hr in individuals with normal renal function. The half-life varied in cases of reduced renal function, with values of 3.9 and 7.0 hr occurring in two subjects with severe renal impairment. Postinfusion serum erythromycin levels were adequately described by two-compartment model kinetics, and values for the distribution volume of the central compartment and the overall distribution are described. Estimated erythromycin distribution volumes in normal individuals may facilitate calculation of absorption efficiencies of erythromycin and its salts after oral doses.

Adult↗
PubMed1978

Hospital use of antimicrobial drugs. Survey at 19 hospitals and results of antimicrobial control program.

Costs and use of antimicrobial agents in 1976 at 19 hospitals were surveyed by review of pharmacy records. Total costs of antimicrobial drugs at individual hospitals ranged from $0.65 to $1.75 per patient day and accounted for 16% to 41% of total pharmacy drug costs. There was marked variation among hospitals in use of specific antimicrobial agents, especially cephalosporins and clindamycin. The cephalosporin and aminoglycoside antibiotics accounted for 66% of the total cost of antimicrobial agents. An 18-month antimicrobial drug control program at one hospital decreased antimicrobial drug costs by 31%. The major effect was in reducing cephalosporin use. The results of the control program document that a significant portion of hospital antimicrobial use is inappropriate and can be eliminated without apparent detriment to patient care.

Anti-Bacterial Agents↗
PubMed1978

Changes in protein binding during disease.

Disease states can alter protein binding of antimicrobials by either a reduction in the concentration of serum proteins or the accumulation of endogenous compounds, such as bilirubin and free fatty acids (FFA), that affect drug-protein interactions. In terms of protein concentration, extremely low levels of albumin (less than 2.5 m/100 ml) are required to markedly reduce binding of antimicrobials. In vitro addition of high concentrations of bilirubin and FFA to normal serum reduces binding of most antimicrobials. However, binding of some antibiotics appears to be enhanced at lower concentrations of FFA probably by an allosteric mechanism. These in vitro observations have been confirmed in sera from patients during heparin administration and patients with hyperbilirubinemia. Reduced protein binding of acidic antimicrobials in uremia appears to be associated with the accumulation of another, as yet unknown, endogenous binding inhibitor. Significant reduction in protein binding can affect the distribution of drugs and results of microbiologic assays.

Anti-Bacterial Agents↗
PubMed1978

Theory and practical impact of binding of antimicrobials to serum proteins and tissue.

Binding of antimicrobials to serum proteins and tissue affects their distribution, elimination and antimicrobial activity. Penetration of drugs into most tissues and interstitial and inflammatory fluids correlates with level of free drug in serum. Serum protein binding can increase or decrease the rate of drug elimination depending on whether total or free drug is available to the excretory or metabolic routes of elimination. Binding to soluble intracellular proteins (ligandin and fatty acid binding protein) appears to be important in the cellular transport and elimination of antimicrobials by renal tubular secretion and hepatic extraction. Although only free, unbound drug is antimicrobially active, the lack of well designed studies has prevented precise quantitation of the influence of binding on therapeutic efficacy in vivo. Pharmacokinetic considerations predict that serum binding greater than 80% would be necessary to significantly reduce free levels of drug in the body. However, extensive protein binding is often compensated for by greater intrinsic activity of lipophilic antimicrobials.

Animals↗
PubMed1978

Enzymuria as a marker of renal injury and disease: studies of N-acetyl-beta-glucosaminidase in the general population and in patients with renal disease.

Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) was shown to be reproducible in random urine specimens when expressed as the ratio of NAG to milligrams of urinary creatinine. The enzyme/creatinine ratio in 815 healthy people was relatively constant throughout childhood and adult life except for the first two years after birth and in individuals 56 years or greater. High ratios in the young children may be explained by low urinary creatinine excretion probably related to small body mass and reduced glomerular filtration rate at this age. The ratio was increased in adult uremic patients and children and adults with a variety of neurologic and obstructive lesions of the voiding mechanism. The presence of bacteriuria did not appear to increase the ratio. Significant enzymuria (greater than 2 SD above the mean for age and sex) was detected in 38 of 81 children with well-characterized renal disease. Among patients with predominantly glomerular disorders there was a close relationship between activity of the disease and enzymuria. In patients with tubulointerstitial disease enzymuria was frequent even in the absence of proteinuria. One of the highest enzyme/creatinine ratios was observed in a child with cystinosis. These studies indicate that NAG enzymuria is a sensitive indicator of activity of renal disease and may prove to be a suitable screening test for significant renal disease or injury in childhood.

Acetylglucosaminidase↗
PubMed1977

Bioavailability of ampicillin and amoxicillin in fasted and nonfasted subjects.

The influence of various test meals and fluid volume on the relative bioavailability of ampicillin and amoxicillin was studied in healthy human subjects. Serum amoxicillin levels were somewhat, but not always, significantly higher than those of ampicillin from equivalent oral doses. Food ingested immediately before dosing reduced serum levels and urinary excretion of both antibiotics to a similar extent. Reduction of dosed water volume caused a marked decrease in serum amoxicillin levels in fasted subjects.

Adult↗
PubMed1977

Pseudomonas aeruginosa bacteremia in a dialysis unit. 11. Relationship to reuse of coils.

Blood for culture was obtained over a six week period from 17 patients undergoing long-term hemodialysis. Bacteremia was detected during 18 of 201 dialyses. Blood drawn during fifteen of these dialyses contained pseudomonas aeruginosa. Ten of the 17 patients (59 per cent) had a Pseudomonas bacteremia some time during the study. Only one patient was symptomatic. The frequency of positive cultures was related to reuse of coils. No cultures were positive until after the fifth use, but by the tenth use, 41 per cent of the dialyses were associated with bacteremia. All coils that were used repeatedly and 32 of 48 of those used only once, grew Ps. aeruginosa when filled with media and incubated. This suggests that the coils were inoculated during dialysis and that benzalkonium chloride, the sterilizing agent, was unable to eradicate this organism. With repeated uses, the number of residual bacteria in the coil became large enough to cause detectable bacteremia during dialysis.

Cross Infection↗
PubMed1977

Persistent effect of antibiotics on Staphylococcus aureus after exposure for limited periods of time.

Persistent suppression of bacterial growth by certain antibiotics was tested by periodic counts of viable organisms in a culture of Staphylococcus aureus that had been incubated in media containing drugs for limited periods of time and then removed by centrifugation. During short (2 hr) periods of exposure of test cultures to penicillin G, cephalothin, erythromycin, clindamycin, vancomycin, and tetracyline, effects on the growth of S. aureus were produced that persisted after removal of the drug for periods of 1.7-4.1 hr. A persistent antibiotic effect was not observed with gentamicin. The persistent effects of penicillin G and erythromycin were directly related to duration of exposure and concentration of drug, up to a point of maximal response. The maximal durations of bacterial suppression after exposure to penicillin G and erythromycin were approximately 2 and 5 hr, respectively. These effects were observed over a wide range of inocula.

Anti-Bacterial Agents↗
PubMed1977

Bioavailability of tetracycline and doxycycline in fasted and nonfasted subjects.

The influence of various test meals and fluid volumes on the relative bioavailability of commercial formulations of doxycycline hyclate and tetracycline hydrochloride was studied in healthy human volunteers. Serum levels of tetracycline were uniformly reduced by approximately 50% by all test meals, whereas serum levels of doxycycline were reduced by 20%. The reduction of tetracycline serum levels will likely be of clinical significance. The bioavailability of each drug was almost identical from an oral solution and from capsules in fasted subjects. The rate of doxycycline absorption was reduced when capsules were administered with a small volume of water, but the overall efficiency of absorption of both drugs was essentially independent of co-administered fluid volume. The use of 8-h serum data provides a reliable estimate of drug bioavailability for tetracycline and, to a lesser extent, for doxycycline.

Adult↗
PubMed1976

Compensating osteotomy at the base of the femoral neck for slipped capital femoral epiphysis.

A compensating osteotomy for correction of the varus and retroversion components of severe slipped capital femoral epiphysis is presented. It is safer than a cuneiform osteotomy done through the callus of the slipped epiphysis because the line of osteotomy is distal to the major blood supply of the posterior retinaculum. The threaded Steinmann pins used for fixation sross both the osteotomy site and the epiphyseal plate, and therefore not only are the mechanical relationships restored, but further slipping is prevented also.

Adolescent↗
PubMed1975

Influence of diet and fluid on bioavailability of theophylline.

The influence of various test meals, and of fluid volumes, on the bioavailability of theophylline from a solid dosage form has been studied in healthy male volunteers. Absorption of a drug was faster after dosing immediately following a high protein meal than after a high fat or a high carbohydrate meal. Absorption from a solution was faster than from a solid dosage form in all treatments; areas under serum level time curves after dosing were also significantly higher up to 12 hr. Areas up to 12 hr after dosing also tended to be higher after the high protein meal and after dosing with 500 ml water on an empty stomach than after other solid dose treatments.

Adult↗
PubMed1975

Prediction of drug dosage in patients with renal failure using data derived from normal subjects.

A one-compartment model designed to predict alterations in persistence of drugs in uremic patients was constructed using information obtained from normal subjects. Data obtained from the literature in which the fraction of absorbed drug eliminated unchanged in the urine and the apparent elimination rate constants were compared in both normal control subjects and in severely uremic patients. Twenty-two drugs were examined. Despite changes in apparent volume of distribution and metabolism reported in uremia, the model was able to predict overall elimination rate constants in severe uremia with an error under 10% for 12 and under 20% for 7 additional drugs. The method appears to be most informative for drugs that tend to be retained in the presence of renal failure. Great error was observed with doxycycline and erythromycin. Studies with erythromycin lactobionate and a cupplate assay reduced the error for this drug from 56% for the glucoheptonate to 18%. Doxycycline is known to have a complex enterohepatic circulation. The model is offered as a useful approach to predict dosage adjustment in uremic patients with drugs for which data are not available.

Cephalosporins↗