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Biomedical subjects

W A Craig

Publications and source records attributed to W A Craig.

At least 127 records · Page 7Linked to original sources
PubMed1980

Cefotaxime pharmacokinetics following a single intravenous dose to patients with varying renal function.

The pharmacokinetics of cefotaxime (HR 756) were investigated in two groups of patients (Groups I and II) with creatinine clearances of greater than or equal to 60 and < 60 ml/min per 1.73 m2 respectively. Each of the 24 patients included in the study received 0.5 g or 1.0 g cefotaxime intravenously as a bolus injection. The decline of serum concentrations was biphasic in all patients, and the data were fitted to the pharmacokinetic two-compartment model. The mean distribution and elimination half-lives of cefotaxime in individuals in Group I were 0.2 and 1.2 hours respectively. In the uremic individuals, the pharmacokinetic parametes did not differ markedly from those in normal subjects, except when renal function was markedly reduced. In severe renal impairment, the elimination half-life increased to 8.3 hours. Cumulative 24-hour urinary excretion accounted for a mean of 59% of the dose in normal individuals, and from 0.3 to 36% of the dose in uremic individuals. Incomplete recovery of intact drug in urine of normal individuals reflects excretion by an extrarenal pathway, possibly as desacetyl cefotaxime. Urine levels were greater than the minimum inhibitory concentrations for susceptible organisms for at least eight hours after dosing in all individuals who produced urine. Because of the relatively small effect of renal impairment on the pharmacokinetics of cefotaxime, dose reduction is necessary only in cases of severe renal impairment.

Aged↗
PubMed1980

Mezlocillin pharmacokinetics after single intravenous doses to patients with varying degrees of renal function.

The pharmacokinetics of mezlocillin were examined after single 2- and 4-g intravenous injections to three groups of male patients with creatinine clearances of I >/= 60, II = 21 to 59, and III </= 20 ml min(-1) 1.73 m(-2). The decline in serum antibiotic levels was biphasic in all groups, and serum data were interpreted in terms of the pharmacokinetic two-compartment model. The mean elimination half-life of mezlocillin after the 2-g dose was 1.3, 1.5, and 2.3 h in groups I, II, and III, respectively. Equivalent values after the 4-g dose were 1.2, 1.6, and 4.4 h. In three functionally anephric patients the mean serum half-life of mezlocillin was 1.5 h during hemodialysis. Mean antibiotic levels in serum were greater than 10 mug ml(-1) for 4 h after the 2- and 4-g doses in group I and 8 h in group II. In group III, levels greater than 10 mug ml(-1) were maintained for 6 h after the 2-g dose and over 12 h after the 4-g dose. Mezlocillin distribution characteristics were largely independent of renal function and dose size. The only observable change occurred in the value of V(dss), which was significantly increased to 0.32 with 0.38 liter kg(-1) in severe renal impairment, compared to ca. 0.2 liter kg(-1) in subjects with normal or slightly impaired renal function. Cumulative 24-h urinary excretion accounted for 50, 40, and 3.2% of the dose in groups I, II, and III, respectively. Urine levels of mezlocillin were uniformly greater than the minimum inhibitory concentration for susceptible organisms for 12 h after dosing in all patients who produced urine. Because of the relatively small increase in the mezlocillin elimination half-life with declining renal function, dose reduction is necessary only in cases of severe renal impairment.

Anti-Bacterial Agents↗
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

Propoxyphene and norpropoxyphene: influence of diet and fluid on plasma levels.

The influence of various test meals and ingested fluid volumes on the bioavailability and pharmacokinetics of propoxyphene and its major metabolite norporpoxyphene has been studied in healthy human subjects. The absorption of drug was delayed by all test meals, but the overall efficiency of absorption was either not affected or was slightly increased. Increased fluid volume intake decreased propoxyphene bioavailability. Plasma levels of metabolite correlated well with levels of unchanged drug, particularly in the first 2 hr after dosing, but were not markedly influenced by treatments.

Adult↗