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Biomedical subjects

W A Craig

Publications and source records attributed to W A Craig.

At least 91 records · Page 5Linked to original sources
PubMed1987

Influence of tablet dissolution on furosemide bioavailability: a bioequivalence study.

In order to evaluate the in vitro dissolution and in vivo bioavailability relationship for furosemide, a bioequivalence study was carried out. Furosemide (40 mg) was administered orally to 12 normal volunteers in a 6 x 6 crossover design using six products (five tablets and one solution) obtained from three pharmaceutical companies. Plasma and urine concentrations of furosemide were quantitated by high-performance liquid chromatography (HPLC). Plasma furosemide profiles were analyzed by non-compartmental methods. Compared to the oral solution, all of the formulations exhibited lower peak furosemide concentrations, longer mean residence times, and, in some cases, diminished bioavailability (range, 66-96%). Similar results were obtained when the reference product (a rapidly dissolving tablet) was used as the standard. All of the products failed the 75/75 rule when compared to either reference standard, apparently because of large intersubject variability. The total amount of furosemide excreted in urine could be associated with the percentage drug dissolved (in vitro) at 30 min. The pH 5.6 dissolution medium (compared to pH 4.6) appears to be an appropriate test medium for assuring batch uniformity and bioequivalence of furosemide products.

Administration, Oral↗
PubMed1987

Post-geriatric evaluation unit follow-up: team versus nonteam.

Twenty-six matched pairs of elderly male patients who had been evaluated in an outpatient geriatric evaluation unit (GEU) were assigned randomly to be followed in either a geriatrics clinic with an interdisciplinary team or a general medical clinic without an interdisciplinary team. Patients were medically stable and living in the community. At 12 months no difference was found in cognitive, affective, or functional status. Both groups of patients had similar frequencies of hospitalization, community placement, use of community services, and number of deaths. These findings suggest that the major benefit from GEUs may be in the initial assessment and treatment rather than in the subsequent care provided by interdisciplinary teams in geriatrics specialty clinics.

Aged↗
PubMed1986

Kinetics of antimicrobial activity.

Assessment of antimicrobial activity from standard in vitro minimum inhibitory and minimum bactericidal concentration determinations alone is incomplete. Rate of bacterial killing, effect of increasing concentration, sub-MIC effects, and degree of suppression of bacterial growth after limited exposure (post-antibiotic effect) more precisely describe the course of antimicrobial activity. Aminoglycoside antibiotics exhibit concentration-dependent bactericidal activity and a prolonged post-antibiotic effect. beta-Lactam antibiotics demonstrate more time-dependent killing and lack post-antibiotic effects, except with staphylococci. Most bacteriostatic antimicrobial agents also produce post-antibiotic suppression of growth. Studies in different animal infection models with a variety of organisms suggest that beta-lactams are more efficacious with continuous dosing, whereas the efficacy of aminoglycosides is relatively independent of dosing regimen, even when administered once daily. Knowledge of the kinetics of antimicrobial action is useful in predicting optimal dosage regimens.

Aminoglycosides↗
PubMed1986

Pharmacokinetic disposition of 14C-glyburide in patients with varying renal function.

The pharmacokinetics of 14C-labeled glyburide were studied in 13 men with varying degrees of renal impairment. Patients received a single, 5 mg oral dose of glyburide as a solution (10 microCi/ml/mg) after a high-carbohydrate breakfast. Serial plasma and breath samples were collected for 48 hours and urine and feces were collected for 5 to 7 days. Patients with normal to moderately impaired renal function (creatinine clearance [CLCR] of 29 to 131 ml/min/1.7 m2) had glyburide plasma t1/2 values of 2.0 to 5.0 hours, with no relationship between CLCR and glyburide clearance. One subject with severe renal impairment (CLCR = 5 ml/min/1.7 m2) had decreased glyburide clearance that resulted in a t1/2 of 11 hours. The elimination of metabolites was more dependent on renal status but was only significantly affected in the patient with severe renal impairment.

Absorption↗
PubMed1986

The in-vivo postantibiotic effect of imipenem and other new antimicrobials.

The postantibiotic effect (PAE) in vivo of imipenem, cefoperazone and latamoxef was investigated in a neutropenic mouse thigh model. Two hours after inoculation of 10(6) cfu of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa into each thigh, the neutropenic mice were treated with single doses of 50-200 mg/kg imipenem, 40-1200 mg/kg cefoperazone and 50-100 mg/kg latamoxef. Serum levels exceeded the MIC for 1.1-2.9 h. Cefoperazone and latamoxef induced PAEs of 2.1-5.6 h for S aureus, but no significant PAEs were induced for the Gram-negative bacilli. In contrast imipenem produced PAE of 0.9-4.6 h with P. aeruginosa. However, strain variation was observed in the duration of the PAE after imipenem. These data are in concordance with the PAEs of the antimicrobials under study when these are determined in vitro. The implications of these findings for clinical use of these drugs need further evaluation.

Animals↗
PubMed1985

Pharmacokinetics of intravenous ceftizoxime in patients on continuous ambulatory peritoneal dialysis.

The pharmacokinetics of ceftizoxime (CZM) were determined in 16 non-infected CAPD patients. Patients received either 500 mg or 1000 mg CZM by i.v. bolus. The dialysate exchange volume was 2 l. Serum CZM concentrations at 10 min were 69.7 +/- 19.7 micrograms/ml (1000 mg dose) and 39.2 +/- 8.4 micrograms/ml (500 mg dose), and declined to 33.7 +/- 13.9 micrograms/ml and 16.9 +/- 3.2 micrograms/ml respectively at 360 min. Dialysate CZM levels at 10 and 360 min were 1.8 +/- 1.3 and 19.9 +/- 6.6 micrograms/ml respectively (1000 mg dose) and 1.4 +/- 0.9 and 12.6 +/- 3.5 micrograms/ml (500 mg dose). The half-time of CZM was 14.1 +/- 4.6 h. Peritoneal clearance of CZM was low and equilibrium was not achieved in 6 h. However peritoneal CZM concentrations were adequate within 1 h for the treatment of most organisms which cause CAPD-related peritonitis.

Adult↗
PubMed1985

Streptococcal myositis.

Two patients had streptococcal myositis. Both patients developed extensive muscle necrosis and overwhelming sepsis after trivial skin trauma. Death occurred within 48 hours of hospital admission despite aggressive surgical and medical treatment. Review of the literature is included to highlight the fulminant nature of this unusual infection and to contrast streptococcal myositis with other soft-tissue streptococcal infections.

Adult↗
PubMed1984

[Dosage interval and in vivo action of penicillin against pneumococci].

The relationship between dosage intervals of penicillin and bactericidal efficacy was investigated in an experimental model using normal and granulocytopenic mice and Streptococcus pneumoniae. Pulsdosing at 4-hour intervals proved to be significantly less efficient than fractional doses of the same total amount of penicillin injected at 1-hour intervals.

Agranulocytosis↗
PubMed1984

Changing patterns of hospital infections: implications for therapy. Changing concepts and new applications of antibiotic pharmacokinetics.

Antibiotics with high protein binding have a lower percentage of free drug available for tissue penetration than antibiotics with lower protein binding. High protein binding, however, may have a beneficial effect on drug distribution. The smaller volume of distribution and reduced glomerular filtration of highly bound agents result in higher serum levels that are sustained longer. Although intermittent and continuous dosing regimens produce similar areas under the concentration-versus-time curves for serum and tissue, intermittent dosing produces higher peak and potentially earlier effective antibiotic levels at the site of infection. The excretion of certain antibiotic agents in the bile may be related to hepatic protein binding, high molecular weight, or unique structural features. Biliary excretion is important not only for bile concentrations but also for dosage modification. Antibiotics with dual elimination by the kidney and biliary tract require minimal dosage modification unless there is concomitant hepatic and renal dysfunction. The third-generation cephalosporins provide good examples of how protein binding, tissue penetration, and excretory mechanisms can be used to alter pharmacokinetics advantageously.

Anti-Bacterial Agents↗
PubMed1983

Impact of dosing intervals on activity of gentamicin and ticarcillin against Pseudomonas aeruginosa in granulocytopenic mice.

The influence of dosing intervals on the activity of gentamicin and ticarcillin against Pseudomonas aeruginosa was studied in vivo. Granulocytopenic mice infected with P. aeruginosa in the thigh muscle were treated with 1-hr or 3-hr injections of gentamicin, ticarcillin, or gentamicin-ticarcillin. Plasma pharmacokinetics of the drugs were correlated with antibacterial activity. Gentamicin injected every 1 hr tended to be less active than gentamicin injected at longer intervals. In contrast, ticarcillin given every 1 hr was significantly more efficacious than equivalent total doses injected every 3 hr. The dosing schedule of gentamicin-ticarcillin was again important for ticarcillin but did not appreciably affect the antibacterial activity of gentamicin. Thus, antimicrobial chemotherapy of P. aeruginosa infections in the granulocytopenic host might be improved by administering ticarcillin rather than gentamicin as a constant infusion.

Agranulocytosis↗
PubMed1983

Pharmacokinetics of piperacillin in subjects with various degrees of renal function.

The pharmacokinetics of piperacillin were examined after single intravenous doses to three groups of male patients with creatinine clearances of greater than or equal to 60 (group I), greater than or equal to 20 but less than 60 (group II), and less than 20 (group III) ml/min per 1.73 m2. Each of 32 patients received either 1 or 4 g of piperacillin as a bolus injection. Three patients received both doses. After a rapid 0.5- to 1-h distribution phase, antibiotic levels in serum declined monoexponentially. After the 1-g dose, mean peak piperacillin levels in serum were 60, 103, and 67 micrograms/ml and the beta phase elimination half-lives were 1.0, 1.6, and 3.9 h in groups I, II, and III, respectively. After the 4-g dose, the respective mean peak piperacillin levels in serum were 329, 232, and 262 micrograms/ml and beta phase half-lives were 1.4, 2.3, and 2.6 h in the three groups. There was no clear evidence of significant dose-dependent effects on any pharmacokinetic parameters in any of the groups. Piperacillin levels in urine were far higher than those in serum, generally exceeding the minimal inhibitory concentrations for susceptible organisms during the 24 h after both the 1- and the 4-g dose. Piperacillin dosage modification is required only in patients with severe renal impairment.

Aged↗
PubMed1983

Cryptococcal meningitis: resolution eight months after antifungal therapy.

A patient with meningitis due to Cryptococcus neoformans had high titers of cryptococcal antigen in her lumbar cerebrospinal fluid after six months of antimicrobial therapy. Antifungal therapy was discontinued after improvement in immunologic parameters occurred. Cryptococcal antigen was no longer detectable in lumbar cerebrospinal fluid eight months after stopping all therapy. Because the course of cryptococcal meningitis is quite variable and cryptococcal polysaccharide is immunosuppressive, recovery of immunologic function may have been coincidental with resolution of the infection rather than due to treatment with transfer factor. However, confirmation of improved immunologic function was helpful in deciding to stop antifungal therapy.

Adult↗
PubMed1982

Correction of drug binding defects in uremia in vitro by anion exchange resin treatment.

Serum protein binding of weakly acidic drugs is impaired in uremia, but that of basic drugs tends to be normal. Treatment of uremic serum with anion exchange resin (Amberlite CG-400, acetate form) corrected binding defects for three acidic drugs (nafcillin, salicylate and sulfamethoxazole) but did not affect the binding of two basic drugs (trimethoprim and quinidine). Resin treatment of normal human serum did not alter the binding of these five drugs. Extraction of the acetate buffer eluate from resin exposed to uremic serum with n-butyl chloride at acidic pH (3.0) resulted in a fraction that could induce similar binding defects in normal human serum. The factor(s) responsible for binding defects in uremia appears to be lipid soluble, weakly acidic, and dialyzable. It is believed to be tightly bound to albumin at physiologic pH, but dissociates from it at acidic pH. These findings further support the previously proposed hypothesis that drug-binding defects in uremia are due to accumulation of certain endogenous metabolic product(s).

Adult↗