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Biomedical subjects

G Carruthers

Publications and source records attributed to G Carruthers.

17 recordsLinked to original sources
PubMed1993

Comparative trial of doxazosin and atenolol on cardiovascular risk reduction in systemic hypertension. The Alpha Beta Canada Trial Group.

The impact of treating hypertension on coronary artery disease has been less than anticipated from epidemiologic studies of cardiovascular risk factors. It has been suggested that adverse effects on lipids of traditional diuretic or beta-blocker regimens may diminish the potential benefits of antihypertensive therapy. Patients with mild to moderate systemic hypertension and normal serum lipids (n = 191) were randomly assigned to doxazosin or atenolol. After dose titration to goal diastolic blood pressure of < or = 90 mm Hg, patients continued treatment for a further 24 weeks. The principal outcome measurement was overall coronary artery disease risk using the Framingham formula. Relative risk of coronary artery disease was reduced to 92.4% of baseline (p = 0.144) for evaluable patients taking atenolol (n = 71), and to 74.6% (p = 0.0001) for patients taking doxazosin (n = 51): atenolol versus doxazosin, p = 0.0074. In patients who met the strict Framingham criteria for age, total cholesterol and high density lipoprotein cholesterol, the relative risk of coronary artery disease for patients taking atenolol (n = 23) was reduced to 86.2% of baseline (p = 0.082), and to 67.4% (p = 0.0004) for patients taking doxazosin (n = 18): atenolol versus doxazosin, p = 0.049. Alpha blockade with doxazosin was more effective than beta blockade with atenolol in reducing the risk of coronary artery disease in hypertensive patients because of the beneficial effects of doxazosin on high-density lipoprotein cholesterol. Overall withdrawal rate was greater in the alpha-blocker group because of a lower response rate and more adverse events.

Adult↗
PubMed1990

A comparison of a controlled release (CR/ZOK) formulation of metoprolol, once daily, with conventional metoprolol tablets, twice daily, in mild to moderate hypertension.

In a randomized double-blind multicenter study in 100 hypertensive patients, the effect of once daily (od) dosing with a new controlled release (CR/ZOK) formulation of metoprolol was compared with that of twice daily (bid) dosing with metoprolol conventional tablets. Eligible patients had a resting seated diastolic blood pressure (DBP) greater than or equal to 95 mm Hg and less than 110 mm Hg at the end of a 6-week open placebo run-in. The active treatment phase lasted 8 weeks. The starting dose was 100 mg od in the CR/ZOK group (N = 53) and 50 mg bid in the tablet group (N = 47). The dose was increased to 200 mg od and 100 mg bid, respectively, in nonresponders (DBP greater than 95 mm Hg) at the end of the first 4-week period. Approximately 40% of both groups received concomitant diuretic therapy throughout the study. The SBP, DBP and HR were reduced compared to baseline in both treatment groups after 4 and 8 weeks. After 4 weeks, 85% of the CR/ZOK group and 74% of the tablet group had DBP less than 95 mm Hg. After another 4 weeks, the corresponding figures were 93% and 93%. There was no statistically significant difference between the treatment groups in the decrease in either SBP, DBP or HR, nor was there any difference in the percentage of responders. Both treatments were equally well tolerated. In conclusion, the antihypertensive effect of once daily dosing (100-200 mg) with the new CR/ZOK formulation of metoprolol is as effective as that of twice daily dosing (50-100 mg) with conventional metoprolol tablets.

Adult↗
PubMed1984

Ethanol-induced inhibition of hepatic uptake of propranolol in perfused rat liver and in man.

Studies were conducted to determine the mechanism whereby ethanol alters the hepatic disposition of propranolol. In eight isolated perfused rat livers, ethanol (mean = 40.1 mmol/l diminished the clearance of dl-propranolol (1.93 +/- 0.43 to 1.24 +/- 0.22 ml/min/g liver, p less than 0.05); increased its t1/2 (12.8 +/- 1.5 to 20.7 +/- 3.25 min, p less than 0.01); and decreased the proportion metabolized (68.7 +/- 4.7% to 34.3 +/- 10.3%, p less than 0.01). These results suggest that ethanol could substantially increase the oral bioavailability of propranolol in humans. However, in normal human volunteers administered 80 mg of propranolol orally, alone, or preceded and followed by ethanol to maintain breath ethanol concentrations of 800-1000 mg/l, increases in propranolol AUC were smaller than anticipated. Seven subjects had increases in free propranolol AUC0-8h (32%, range: 12-61%) (p less than 0.05), while total propranolol AUC0-8h increased by a mean 22% (range: -4-+49%). Propranolol free fraction varied with time and was higher after ethanol (mean = 0.090 vs 0.084) (p less than 0.077). The extent of the propranolol-induced slowing of heart rate was not influenced by ethanol (mean decrease from baseline of 13 bpm at peak propranolol effect vs 9 bpm without ethanol); mean heart rates following propranolol with ethanol were higher at all times (mean of 7.5 bpm) (p less than 0.001) than after propranolol alone. Ethanol inhibits the hepatic oxidative metabolism of propranolol in vitro; however, any effect on heart rate of higher concentrations of propranolol induced by ethanol in humans is offset by the cardio-acceleratory effect of ethanol.

Animals↗
PubMed1984

Pharmacokinetics of the major metabolites of D-penicillamine in patients with rheumatoid arthritis.

The pharmacokinetic disposition of D-penicillamine and its major metabolites, penicillamine cysteine disulfide ( PSSC ) and penicillamine disulfide ( PSSP ) has been studied in eight patients with rheumatoid arthritis. Plasma concentrations of D-penicillamine, PSSP and PSSC displayed similar characteristics in terms of times to maximum concentrations and biphasic elimination from plasma. Initial t1/2 (alpha) phase ranged from 0.86 to 4.41 h for parent drug and 0.81 to 4.41 h for metabolites. Final t1/2 (beta phase) ranged from 3.4 to 9.45 h for D-penicillamine and 5.62 to 21.7 h for the metabolites. Total drug and metabolites detected in urine accounted for 12.0 to 48.7% of oral drug.

Adult↗
PubMed1983

Conversion in vitro of urinary (+)-penicillamine to its major metabolites, PSSP and PSSC.

To investigate the discrepancy between the apparent pharmacokinetic disposition of (+)-penicillamine in plasma and urine, the spontaneous degradation of (+)-penicillamine was studied in acidified and non-acidified urine. Degradation was prevented by acidification. The oxidized metabolites were converted to reduced (+)-penicillamine by electrolysis.

Biotransformation↗
PubMed1981

Immunological and pharmacological monitoring in the clinical use of cyclosporin A.

Immunological reactivity to donor antigens and serum concentrations of cyclosporin A were monitored in six patients after renal transplantation. At concentrations of 0.1--1.0 microgram/ml cyclosporin A prevented both donor-specific immune reactivity and clinical rejection during the early post-transplant course. Measurement of cyclosporin A levels and immunological indices allowed individual adjustment of the dosage so as to give excellent early graft function with few adverse effects.

Cyclosporins↗