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Biomedical subjects

G A Gibson

Publications and source records attributed to G A Gibson.

35 records · Page 2Linked to original sources
PubMed1987

Relationship of steady-state serum concentrations of amiodarone and desethylamiodarone to therapeutic efficacy and adverse effects.

The relationship of steady-state serum levels of amiodarone and its major metabolite, desethylamiodarone, to therapeutic and toxic effects was evaluated in 111 patients treated for supraventricular and ventricular arrhythmias. All patients were treated for more than two months (mean 10 +/- 7), and repeated serum levels determined at least two months apart were within 0.5 mg/liter of each other. Effective control of arrhythmias during steady-state therapy was achieved in 91 patients (82 percent of the study populations); recurrent arrhythmias or sudden death did not correlate with levels. An adverse drug effect necessitating cessation of therapy and/or concomitant medical therapy for the adverse effect occurred in 12 patients (11 percent); an additional 33 patients (30 percent) had an adverse effect that did not require change in therapy. The mean serum concentrations of amiodarone and desethylamiodarone associated with adverse drug effects were higher (2.6 +/- 1.2 mg/liter and 2.0 +/- 0.8 mg/liter) than those in patients without adverse effects (2.1 +/- 1.0 mg/liter and 1.5 +/- 0.7 mg/liter), p less than 0.05. An amiodarone serum concentration of 2.5 mg/liter or more had a positive predictive value of 76 percent for identifying patients with an adverse effect. The level of desethyl metabolite of amiodarone correlated directly with the serum amiodarone concentration (r = 0.82). Measurement of desethylamiodarone did not increase the sensitivity or specificity of the amiodarone level alone in the identification of patients at risk for adverse drug effects.

Adult↗
PubMed1987

Biliary excretion of imipenem-cilastatin in hospitalized patients.

Imipenem-cilastatin concentrations in bile were measured in 12 cholecystectomy patients (group 1) and 12 patients with common duct drainage (group 2). Six patients in each group received 0.5 g, and six received 1.0 g intravenously over 30 to 60 min. In group 1, bile was collected a mean of 85 min postinfusion. The mean concentrations of imipenem in bile were 1.3 microgram/ml after the 0.5-g dose and 3.5 micrograms/ml after the 1.0-g dose. The mean concentrations of cilastatin in bile were 9.0 micrograms/ml after the 0.5-g dose and 38.0 micrograms/ml after the 1.0-g dose. In patients with common duct drainage, bile was collected predose and 0 to 2, 2 to 3, 3 to 4, and 4 to 6 h postinfusion. Peak imipenem concentrations in bile were 4.4 micrograms/ml after the 0.5-g dose and 8.6 micrograms/ml after the 1.0-g dose. Peak cilastatin concentrations in bile were 4.6 micrograms/ml for the 0.5-g dose and 10.9 micrograms/ml for the 1.0-g dose. Peak imipenem concentrations in bile occurred a mean of 2.3 h after administration of the drug; cilastatin peak concentrations occurred at a mean of 2.4 h. Less than 0.3% of each drug was recovered in the bile. Our results suggest that imipenem enters bile by simple diffusion and in most patients attains concentrations sufficient to inhibit susceptible organisms. In contrast, cilastatin had a bimodal entry into bile. Some patients had very high concentrations in bile, whereas others had very low or undetectable concentrations, suggesting that cilastatin may be actively secreted into the bile.

Adult↗
PubMed1986

Imipenem pharmacokinetics and body fluid concentrations in patients receiving high-dose treatment for serious infections.

Serum, urine, tissue, and body fluids were collected from 40 adult patients who were receiving imipenem/cilastatin treatment for serious infections. Thirty-two patients were given 1 g every 6 h (4 g/day), and eight received 500 mg (2 g/day). Mean peak concentrations in serum were 34.9 +/- 4.0 micrograms/ml for the 1-g dose and 26.6 +/- 2.5 micrograms/ml for the 500-mg dose. Trough levels were 3.1 and 1.0 micrograms/ml, respectively. No evidence of drug accumulation was found after comparing peaks measured early in the treatment with those measured late. Peak levels were only marginally increased when infusions were given over 30 versus 60 min. The mean serum half-life was 82.0 +/- 25.3 min, with a range of 50 to 138 min. The apparent volume of distribution was 0.35 +/- 0.13 liter/kg, and the mean total body clearance was 0.183 +/- 0.067 liter/kg per h. Creatinine clearance correlated directly with the plasma elimination rate and inversely with the serum half-life. Moreover, total body clearance fell as the age of the patient rose. The mean urinary recovery was 39.1 +/- 12.8% (range, 15.0 to 59.2%) and did not correlate with creatinine clearance until it was below 15 ml/min. Of 20 specimens of various gastrointestinal secretions, 13 had imipenem concentrations that were low, but above the MIC for most resident flora. Pus, sputum, and bone all had concentrations of the drug sufficient to inhibit the infecting organisms, and these levels reflected generally excellent clinical responses.

Adult↗
PubMed1985

Influence of high-dose pentobarbital on theophylline pharmacokinetics: a case report.

The effect of high dose pentobarbital coma therapy on the total body clearance of theophylline (CLT) was evaluated in a neurosurgical patient. Preinduction and induction CLT were 4.22 and 8.02 L/h, respectively, which represented a 95% increase in the CLT as a consequence of pentobarbital therapy. Although barbiturates have been shown to induce hepatic microsomal enzymes, previous reports minimize their effect on CLT in humans. This case report demonstrates remarkable alterations in the CLT as a result of high doses of pentobarbital, necessitating the need for substantial dosage adjustments of theophylline.

Aminophylline↗
PubMed1985

Safety and efficacy of high-dose treatment with imipenem-cilastatin in seriously ill patients.

Imipenem-cilastatin was given in doses of 1 g intravenously every 6 h to 31 patients. Twenty-five patients, with 27 infections, were clinically evaluable and received 20 to 210 g of imipenem for a duration of 5 to 56 days (average 16.3 days). Infections included seven cases of osteomyelitis, seven of bacteremia, five of cellulitis, two of pneumonia, three of pelvic cellulitis, two of intraabdominal abscess, and one each of empyema, mediastinitis, and endometritis. Fifty-five percent of the infections were caused by gram-negative bacilli, 33% were due to gram-positive organisms, and 10% were caused by anaerobes. Twenty-two patients (81%) were cured, three improved, one relapsed, and one became superinfected with a resistant organism. In 5 of 11 cases with Pseudomonas aeruginosa, the imipenem MIC for organisms isolated by the end of treatment was higher than it was initially, raising concern that imipenem should not be used alone to treat Pseudomonas aeruginosa infections. Twenty-one patients had no adverse reaction; of the remaining 10 patients, 4 had nausea, 1 had urticaria, and 6 had mild abnormalities in hepatic function; three episodes of diarrhea included two with Clostridium difficile toxin in stool and one with pseudomembranous colitis, as determined by sigmoidoscopy. Levels of creatinine, hemoglobin, leukocytes, platelets, prothrombin, and urine components were unchanged. Imipenem-cilastatin is a clinically effective antibiotic with freedom from nephrotoxicity and hematological abnormalities in the large doses used in this study.

Adult↗
PubMed1982

Obtaining reimbursement for clinical pharmacokinetic monitoring.

A method of obtaining reimbursement for clinical pharmacokinetic monitoring is described. The process included reviewing the existing literature, observing the practices of others providing similar services, collecting workload and expense data, selecting an equitable fee, and presenting third party payers with evidence of the service's need, documentation, and effectiveness. The average patient was monitored by the pharmacokinetic service for 8.4 days and had 5.1 serum samples drawn. The physician received 3.1 dosing recommendations. An average of 4.3 hours was spent monitoring each patient with an average cost of $86. Of the several alternatives for charging considered, an inclusive charge of $10 per patient day was chosen. Blue Cross reimbursement criteria for pharmacokinetic monitoring stipulated that (1) the service must be physician initiated; (2) documentation of services provided must appear as a permanent part of the patient's record; (3) service provided must be identified with a specific group of patients rather than applied equally to all patients in the institution; and (4) evidence of reduced morbidity, mortality, or length of hospital stay would help. During 1981, $37,470 in charges was generated for pharmacokinetic monitoring services with reimbursement being received from third party programs, insurance companies, and private patients.

Humans↗
PubMed1981

Estimating creatinine clearance in morbidity obese patients.

Estimates of creatinine clearance (Clcr), using five methods, were compared to measured Clcr in morbidity obese patients. Patients whose total body weight (TBW) was greater than or equal to 195% of their ideal body weight (IBW) and who had urinary Clcr measured with 24-hour urine collections were studied. The 12 men weighed an average of 180 kg; the 31 women averaged 138 kg. The methods studied considered a combination of the following factors: weight, age, sex, and serum creatinine. One method was a nomogram; TBW could not be used because of limitations of the nomogram. Both TBW and IBW were used in two methods that considered weight as a variable. Measured Clcr averaged 105.7 ml/min/1.73 sq m body surface area. All estimating methods using IBW significantly underestimated Clcr; all methods using TBW significantly overestimated Clcr. Two methods that did not include body weight as a variable predicted Clcr more accurately than did other methods, but there was still a significant difference between estimated and measured Clcr. None of the Clcr estimation methods is accurate in morbidly obese patients.

Adult↗
PubMedDate not supplied

Naloxone-responsive hypotension in a patient with an ACTH-secreting tumor.

We report a case in which hypotension was corrected by the administration of naloxone in a patient with an ACTH-secreting mediastinal tumor. According to previous reports, reversal of hypotension would not be expected in patients with suppressed central ACTH secretion. The implications of this patient's response on the possible mechanisms for naloxone's action in reversing septic shock are discussed.

Adrenocorticotropic Hormone↗