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Biomedical subjects

D Duffin

Publications and source records attributed to D Duffin.

9 recordsLinked to original sources
PubMed1992

Drug-patient interactions and their relevance in the treatment of heart failure.

The effects of congestive heart failure (CHF) on drug disposition and elimination are many and varied. Indeed, the pharmacokinetics of many of the drugs used to treat CHF are significantly altered by the patient's underlying condition. Reduced gastric emptying in CHF delays absorption and decreases the peak plasma concentrations of furosemide, bumetanide, and digoxin. Moreover, drugs that have a high hepatic extraction ratio (organic nitrates, morphine, prazosin, and hydralazine) achieve higher than expected plasma concentrations in patients with CHF. In contrast, drugs requiring biotransformation to active forms, e.g., angiotensin-converting enzyme (ACE) inhibitors such as enalapril, perindopril, quinapril, and ramipril, generally have lower than expected plasma concentrations. Nevertheless, ACE inhibitors can impair renal function in CHF, leading to an actual increase in plasma concentrations. However, decreases in absorption and first-pass metabolism are often offset by reduced hepatic and renal clearance. The overall absorption of lisinopril may be reduced in some CHF patients; consequently, the onset of effect is delayed but is often more prolonged.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

A double blind comparative study of lisinopril and enalapril in patients with essential hypertension.

The efficacy and safety profiles of lisinopril (10-40 mg) and enalapril (5-20 mg) were compared in 169 hypertensive patients during 12 weeks' treatment in a randomised double-blind parallel group study. BP was measured hourly for the first 8 hours following the first dose of lisinopril 10 mg and enalapril 5 mg. The peak reduction in sitting systolic and diastolic BP occurred approximately 6 hours post dose in both groups. At 8 hours post dose lisinopril had reduced sitting systolic and diastolic BP by 2.9 mmHg and 3.5 mmHg (P = 0.02) respectively, more than enalapril with similar results for standing BP. One patient on enalapril developed first dose postural hypotension. After 12 weeks' therapy lisinopril produced a greater decrease (P less than 0.05) in BP than enalapril. Sitting BP decreased by 25/15 mmHg on lisinopril and 17/12 mmHg with enalapril. Standing BP decreased by 24/14 mmHg compared with 16/10 mmHg on enalapril. Eighteen patients did not complete the study, 8 on lisinopril (6 adverse events, 1 uncontrolled BP, 1 protocol violator) and 10 on enalapril (8 adverse events, 1 uncontrolled BP, 1 protocol violator). Overall, the results indicated that while both drugs are well tolerated, the dose range of lisinopril 10-40 mg may produce a greater antihypertensive effect than enalapril 5-20 mg.

Adult↗
PubMed1991

Low-dose cyclopenthiazide in the treatment of hypertension: a one-year community-based study.

After an 8-week placebo period, 73 patients whose diastolic blood pressures were between 90 and 110 mmHg were randomly assigned to receive 125 micrograms (low dose) or 500 micrograms of cyclopenthiazide (standard dose) for a period of one year. Blood pressure was measured in the patient's home by the same observer at two-weekly intervals during an 8-week placebo run-in period, every 4 weeks for a further 12 weeks and at 24, 36 and 52 weeks thereafter. Serum potassium, urate, glucose, glycosylated haemoglobin, total and HDL cholesterol, and apolipoproteins were measured at the end of the placebo period and at 4, 8, 24 and 52 weeks of active treatment. Twelve of the 73 patients had an inadequate antihypertensive response--five on the higher dose and seven on the lower dose. One patient receiving 500 micrograms was withdrawn because of adverse effects. In the remaining 60 patients, systolic and diastolic blood pressures were significantly reduced when compared with pretreatment values in both treatment groups throughout the one year period. The decreases in blood pressure were not significantly different from each other (p greater than 0.65). Three patients on 500 micrograms required potassium supplements. Maximum decreases in the serum potassium of 0.52 mmol/l (500 micrograms dose) and 0.14 mmol/l (125 micrograms dose) were observed at 24 weeks of treatment in the remaining 57 patients. The differences between the two doses at this time were statistically significant (p less than 0.05), as were the increases in serum urate observed at 4, 8 and 24 weeks (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Characterization of macrophage recognition and killing of SV40-transformed tumor cells that are "resistant" or "susceptible" to contact-mediated killing.

In this report we used the macrophage-"resistant" and -"susceptible" cell lines, F5m and F5b, to determine why AKR or AKR-like virus expression makes the F5m cell line more resistant to in vitro macrophage killing than the F5b cell line. We found that resistance to macrophage killing may be transmitted by an infectious AKR or AKR-like murine leukemia virus and that resistance was concomitant with virus expression as measured by the presence of AKR virus-specific 70 kDa glycoprotein. We report that macrophage cytotoxicity of these cell lines is dependent upon the direct contact between tumor cells and macrophages. In contrast, macrophage-mediated cytostasis occurred via soluble macrophage products and no differential susceptibility of F5b or F5m to macrophage-mediated cytostasis was observed. Macrophage binding of F5b was also significantly better than that of F5m. These data suggest that only the events that depend upon the close contact of macrophages and tumor cells will be affected by the expression of AKR or AKR-like virus. Therefore, the differences in susceptibility of F5m and F5b to direct macrophage-mediated cytotoxicity are apparently because the macrophage binding of F5m is less efficient than the binding of F5b.

AKR murine leukemia virus↗
PubMed1984

Circadian variation in plasma theophylline concentrations during maintenance therapy with a sustained-release preparation in patients with obstructive airways disease.

Circadian variation in plasma theophylline concentrations was studied in eight patients with obstructive airways disease during regular 12-hourly dosing at 09.00 and 21.00 h with a sustained-release theophylline formulation. After regular dosing for a minimum period of 3 days, plasma concentration measurements were made at 09.00, 13.00, 21.00 and 01.00 h on 3 consecutive days and at more regular intervals during a complete 24 h period on day 4. On each day, theophylline concentrations for the first 4 h of the dosing interval were consistently higher during the day than at night. However, the differences were significant only at 13.00/01.00 h on day 2, and for each of the first 4 h on day 4. On day 4, following the dose at 21.00 h the mean peak plasma theophylline concentration occurred 6.9 +/- 0.8 h after dosing; in contrast, after the morning dose the mean peak concentration occurred at 4.5 +/- 0.8 h. However, the mean 'steady-state' concentrations during the two dose intervals were not significantly different. Thus circadian variations in plasma drug concentrations do occur in patients taking maintenance theophylline therapy: differing rates of absorption may account for the observed pattern.

Aged↗
PubMed1983

Investigation of diurnal changes in the disposition of theophylline.

The mechanism of observed temporal variations in plasma theophylline concentrations has been investigated. Eight healthy volunteers were given both oral and intravenous doses of theophylline (5 mg/kg) at 09.00 h and 21.00 h under controlled conditions. Regular plasma concentration measurements were made following each dose in order to determine the diurnal and nocturnal disposition of the drug. Plasma theophylline concentrations at 0.5 h following each oral dose were 6.9 +/- 0.8 micrograms/ml, a.m., and 3.9 +/- 0.6 microgram/ml, p.m. (P less than 0.05). Time to peak concentration was 1.69 +/- 0.28 h, a.m.; 2.13 +/- 0.23 h, p.m. (P less than 0.05). Values for ka were not significantly different, however. Overall bioavailability, volume of distribution and systemic clearances, calculated for the 12 h period after each dose, did not differ significantly between day and night. Diurnal variations in theophylline disposition do not appear to be the result of changes in metabolism or excretion, but may reflect minor differences in absorption.

Administration, Oral↗