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Biomedical subjects

J Aberg

Publications and source records attributed to J Aberg.

At least 19 recordsLinked to original sources
PubMed2001

Effect of ritonavir/saquinavir on stereoselective pharmacokinetics of methadone: results of AIDS Clinical Trials Group (ACTG) 401.

UNLABELLED: The effect of ritonavir 400 mg/saquinavir 400 mg twice daily on the stereoselective pharmacokinetics of methadone was examined in 12 HIV-infected, methadone-using study subjects. DESIGN: A 24-hour methadone pharmacokinetic study was performed before antiretroviral therapy was begun and after 15 days of therapy. Methadone concentration was measured by a chiral plasma assay because the drug is administered as a racemic mixture of R- and S-methadone, but only the R-isomer is active. Both changes in plasma protein binding and changes in objective and subjective opioid effect were monitored. RESULTS: Ritonavir/saquinavir administration was associated with 40% decrease in total S-methadone AUC0-24hr and 32% decrease in R-methadone area under the curve (AUC)0-24hr, and both changes were statistically significant (p =.001 for both). When AUC was corrected for the changes in protein binding induced by ritonavir/saquinavir, R-methadone free AUC0-24hr decreased 19.6% whereas the S-methadone decreased 24.6%, neither of these changes was statistically significant (p =.129 and p =.0537, respectively). This change in methadone exposure was not associated with any evidence of withdrawal from narcotics and no modification of methadone dose was required. CONCLUSIONS: Our data indicate that ritonavir/saquinavir administration is associated with induction of metabolism of methadone but this is greater for the inactive S-methadone. However, approximately 37% of the decrease in the total R-methadone exposure can be explained by protein binding displacement. Ritonavir/saquinavir can be used in HIV-infected people taking methadone without routine dose adjustments.

Adult↗
PubMed2001

Dose-related effects of metoprolol on heart rate and pharmacokinetics in heart failure.

BACKGROUND: The pharmacokinetics and pharmacodynamics of immediate-release (IR) metoprolol, 50 mg 3 times daily, were compared with those of different doses of controlled-release/extended-release metoprolol (CR/XL) given once daily. METHODS AND RESULTS: Fifteen patients with chronic heart failure were randomized to a 3-way crossover study to receive metoprolol IR 50 mg 3 times daily, CR/XL 100 mg once daily, and CR/XL 200 mg once daily for 7 days. On the seventh day of each treatment, serial plasma samples were drawn and standardized exercise tests and a 24-hour Holter recording were performed. Metoprolol IR 50 mg produced peak plasma levels comparable to those observed for CR/XL 200 mg (285 v 263 nmol/L). The difference in mean 24-hour heart rate between CR/XL 100 mg and IR 50 mg was 1.0 bpm (95% confidence interval [CI]), -2.9 to 4.9; NS) compared with -3.8 bpm (95% CI, -7.6 to -0.04; P = .048) between CR/XL 200 mg and IR 50 mg. Submaximal exercise heart rate was lower for patients receiving CR/XL 200 mg than those receiving IR 50 mg. No difference in tolerance or exercise performance was observed between treatment regimens. CONCLUSIONS: Peak plasma levels produced by metoprolol 200 mg CR/XL were similar to those of 50 mg IR. Metoprolol CR/XL 200 mg was associated with a more pronounced suppression of heart rate than metoprolol IR 50 mg. It is suggested that patients can safely be switched from multiple dosing of metoprolol IR 50 mg to a once-daily dose of metoprolol CR/XL.

Adrenergic beta-Antagonists↗
PubMed2000

Left ventricular systolic and diastolic function and exercise testing in primary hyperparathyroidism-effects of parathyroidectomy.

BACKGROUND: Nontraditional manifestations of primary hyperparathyroidism (HPT) are controversial and may include morbidity, mortality, and risk factors for cardiovascular diseases. This study evaluates cardiovascular functions at rest and during exercise in HPT. METHOD: Thirty patients with HPT (mean serum calcium, 2.97 +/- 0.24 mmol/L) and 30 control people with normocalcemia, matched for age and sex, underwent symptom-limited exercise testing and echocardiography before and 13 months (mean) after having a parathyroidectomy. RESULTS: Despite similar maximal workload and blood pressures at rest in patients and healthy controls, HPT associated with higher systolic blood pressure during exercise (P =.03) and increased number of ventricular extrasystolic beats (P =.04). There was also an operatively reversible increase in ST-segment depression during exercise. Echocardiography showed an increased left ventricular (LV) isovolemic relaxation time (P =.02) and mitral deceleration time (P =.08), which indicate an LV diastolic dysfunction that could be partially reversed by operation. LV systolic function (ejection fraction and shortening fraction) tended to be elevated in HPT (P =.07 and.06, respectively) and diminished after parathyroidectomy. There was a trend toward higher LV mass, especially among the men with HPT (P =.06), which was unchanged postoperatively. CONCLUSIONS: HPT couples to reversible signs of myocardial ischemia and LV dysfunctions with a possible increased risk of life-threatening arrhythmia.

Adult↗
PubMed1999

Endothelial vasodilatory dysfunction in primary hyperparathyroidism is reversed after parathyroidectomy.

BACKGROUND: Primary hyperparathyroidism (HPT) is accompanied by hypertension and a cardiovascular mortality. Impaired endothelium-dependent vasodilatation (EDV) occurs in hypertension but has not been fully investigated in HPT despite the vasoactive influences of parathyroid hormone. METHODS: Twenty-five HPT patients and 25 normocalcemic control subjects, matched for age and gender, underwent forearm venous occlusion plethysmography. EDV and endothelium-independent vasodilatation (EIDV) were evaluated during local infusion of metacholine (2 and 4 micrograms/min) and nitroprusside (5 and 10 micrograms/min), respectively. The endothelial function index was calculated as the ratio of forearm blood flows during the high doses of metacholine and nitroprusside. Ambulatory 24-hour blood pressures and thickness of the intima-media complex of the carotid arteries were also measured; the latter is considered an early marker of atherosclerosis. RESULTS: Endothelial function index was lower in the HPT patients compared with control subjects (1.01 +/- 0.26 vs 1.27 +/- 0.31, P = .003). Reinvestigation 10 months after parathyroidectomy showed normalization of the index (1.31 +/- 0.39, P = .01) due to a numeric increase in EDV and decrease in EIDV. The carotid intima-media thickness and blood pressure were similar in the groups and unaltered postoperatively. CONCLUSIONS: Endothelial vasodilatory dysfunction is another indicator of the vascular disturbance of HPT and can be normalized by parathyroidectomy.

Aged↗
PubMed1999

Natural history of intestinal microsporidiosis among patients infected with human immunodeficiency virus.

A chart review of 73 human immunodeficiency virus (HIV)-infected patients with enteric microsporidiosis was conducted to define the natural history of microsporidiosis. A substantial proportion of patients remained symptomatic after 6 months (54.8% with persistent diarrhea and 51.2% with weight loss). Predictors for persistent diarrhea included high HIV RNA viral load and no initiation of protease inhibitor therapy.

AIDS-Related Opportunistic Infections↗
PubMed1998

Haemodynamic and renal effects of felodipine in young and elderly subjects.

OBJECTIVE: To study the influence of age on renal and haemodynamic effects of the calcium antagonist felodipine. METHODS: Eight young (mean age 27 years) and eight elderly (mean age 75 years) healthy normotensive subjects were given felodipine intravenously for 120 min aiming at close to therapeutic plasma level concentration. Renal blood flow (RBF) and renal vascular resistance (RVR) was estimated from para-aminohippuric acid (PAH) clearance 51CrEDTA clearance was used to measure glomerular filtration rate (GFR) and used in the calculations of fractional excretion (FE) of electrolytes. Impedance cardiography was performed to assess stroke volume and for the calculation of cardiac output and ejection fraction. RESULTS: At the end of felodipine infusion, the concentration of felodipine was on average 10.0 nmol x l(-1) in young and 12.0 nmol x l(-1) in elderly subjects (NS). During felodipine infusion blood pressure (BP) decreased from 138/76 to 120/68 in elderly subjects. The BP in young subjects was 126/74 at basal and 125/70 after infusion of felodipine. The systemic and renal vascular resistance decreased to a similar extent in young and elderly subjects after felodipine infusion. Felodipine caused a decrease in systemic vascular resistance from 25.6 to 23.3 in elderly and from 23.8 to 21.8 in the young subjects. Mean values for RVR at baseline and during infusion of felodipine were significantly higher in the elderly (10.1-15.1) than in the young subjects (5.4-6.7). Felodipine reduced RVR by 10% in the young and by 12% in the elderly at the end of infusion. The young subjects had 31% higher GFR than the elderly subjects at the start of infusion. Felodipine infusion did not affect GFR. There were no effects on stroke volume and ejection fraction. An initial natriuretic effect was found after infusion of felodipine in the young subjects. The fractional excretion of all electrolytes tended to increase after both felodipine and placebo, more in the elderly than in the young subjects. CONCLUSION: The effects of felodipine on central and renal haemodynamics previously observed in young and middle-aged subjects also seem to exist in the elderly. Volume expansion seems to increase the excretion of electrolytes more in elderly than in young people, and therefore the effect of felodipine on natriuresis is more evident in young subjects.

Adult↗
PubMed1997

Bioequivalence, pharmacokinetic and pharmacodynamic response to combined extended release formulations of felodipine and metoprolol in healthy volunteers.

OBJECTIVE: The primary aim of this study was to investigate whether bioequivalence is achieved for a new fixed combination of extended-release (ER) felodipine and controlled-release (CR/ZOK) metoprolol compared with the free combination of felodipine ER metoprolol CR/ZOK. The second aim was to study whether there was an interaction in pharmacokinetics and pharmacodynamics between felodipine and metoprolol when administered as ER formulation. METHODS: Two four-way cross-over studies were performed in 36 young subjects and 24 elderly subjects with frequent measurement of drug plasma concentrations, blood pressures and heart rate. The pharmacokinetic analysis included enantioselective analysis in six subjects. RESULTS: Bioequivalence between the fixed combination and the free combination was observed for the two drugs (mean difference 27%) except for a minor deviation regarding Cmax of metoprolol in the elderly. No significant interaction was shown except for a small increase (6%) of metoprolol AUC in the younger subjects. Mean plasma S-/R-enantiomer ratios were almost identical for the different treatments. Blood pressure and heart rate was significantly reduced for the fixed combination compared with felodipine ER in the younger and the elderly subjects. No significant difference regarding pharmacodynamics was detected between the fixed combination and the corresponding free combination. CONCLUSION: The fixed combination consistently provides fairly constant and effective felodipine and metoprolol concentrations after once-daily administration of one tablet. It is clinically interchangeable with the free combination of metoprolol CR/ZOK tablets and felodipine ER tablets. Finally, felodipine and metoprolol do not interact on a pharmacokinetic level when administered as the fixed combination.

Adrenergic beta-Antagonists↗
PubMed1993

Method for studying drug-warfarin interactions.

The potential effects of extended-release felodipine on the pharmacokinetics and pharmacodynamics of warfarin were studied in a double-blind crossover study in 12 healthy men. Warfarin dosage was adjusted to achieve stable subtherapeutic anticoagulation. Subjects were then randomized to receive 2 weeks of treatment with 10 mg extended-release felodipine or placebo once daily, and warfarin dosage was adjusted if necessary to maintain stable international normalized ratio. The pharmacokinetics of R- and S-warfarin and the warfarin dose requirement did not differ importantly between periods of treatment with felodipine and placebo. The design of this study is suitable for general use in the identification of possible effects of other drugs on the pharmacokinetics and pharmacodynamics of warfarin. A different approach is needed if there is any reason to expect that warfarin may alter the pharmacokinetics or pharmacodynamics of the test drug.

Adult↗
PubMed1992

Electropharmacologic effects and pharmacokinetics of almokalant, a new class III antiarrhythmic, in patients with healed or healing myocardial infarcts and complex ventricular arrhythmias.

The electropharmacologic effects and pharmacokinetics of almokalant, a new class III antiarrhythmic, were investigated in a randomized, placebo-controlled, double-blind study, and efficacy was evaluated. Ten post-myocardial infarction patients with complex ventricular arrhythmias were included and received, in randomized order on consecutive days, 4.5 mg (12.8 mumol) of almokalant or placebo intravenously over 10 minutes. One patient received infusion at a higher rate and developed self-terminating torsades de pointes. In the remaining 9 patients the corrected QT interval increased significantly: At the end of placebo infusion the corrected QT was 445 +/- 18 ms and after almokalant 548 +/- 53 ms (p = 0.0015). The signal-averaged electrocardiographic parameters did not change. The number of ventricular premature complexes decreased significantly during the first 15 minutes after almokalant infusion (p = 0.04). No additional proarrhythmic or other significant adverse events were noted. The almokalant plasma concentration showed a biphasic decrease with an elimination half-life of 2.4 +/- 0.1 hours. Almokalant was rapidly cleared from the body with a clearance of 11 +/- 1 ml/min/kg. When given with certain precautions almokalant appears safe and well-tolerated and may be antiarrhythmic by prolonging refractoriness.

Adult↗
PubMed1991

Pharmacokinetics of felodipine in chronic hemodialysis patients.

Five chronic hemodialysis patients (1 woman and 4 men, aged, 46-68 yr) were given an oral dose of 10 mg felodipine followed by 0.057 mg [3H] felodipine IV. After 5 hours, a hemodialysis treatment lasting 4 hours was performed. Blood and dialysate flows were 200 mL/min and 500 mL/min, respectively. Capillary dialyzers with 1.3 m2 cellulose acetate membrane were used. The pharmacokinetic characteristics and reduction in diastolic BP were similar to those in hypertensive patients with normal renal function and in uremic patients who were not treated with dialysis. There was no measurable removal of felodipine by hemodialysis. Dialyzer clearance of radioactive metabolites was about 10 mL/min, and only 8.9% of the dose was eliminated by the treatment. The half-life of radioactive metabolites was 10 days (6-14 days) in three patients dialyzed thrice weekly. Since the metabolites are biologically inactive, no adjustment of dose is required in hemodialysis patients.

Administration, Oral↗
PubMed1990

Acute and steady-state pharmacokinetics and antihypertensive effects of felodipine in patients with normal and impaired renal function.

Eighteen patients (14 men and 4 women, aged 36-74 years) treated with metoprolol for a month were included in the study. Twelve had impaired renal function (IRF) with a glomerular filtration rate (GFR) of 7.5-77.1 mL/min and six having normal renal function (NRF) with a GFR of 84.9-113.0 mL/min. Plasma and urine concentrations of felodipine and metabolites, heart rate, and blood pressure were recorded over 24 hours on day 1 after an oral dose of 10 mg felodipine and 0.04 mg 3H-felodipine IV and repeated on day 29 during continuous treatment with felodipine, 10 mg bid. The bioavailability of the oral dose on day 1 and day 29 was 13% and 12.5%, respectively. The terminal plasma half-life (t1/2) on day 29 was 22 hours and systemic clearance was 490 mL/min on day 1 and 434 mL/min on day 29 (NS). There were no differences in these parameters between NRF and IRF. The protein binding determined by equilibrium dialysis in the six patients with the lowest GFR was 99.74% on day 1 and 99.73% on day 29 and did not differ significantly from previously reported values in healthy subjects. The mean supine blood pressure before the acute dose of felodipine was 164/96 mm Hg in the IRF patients and 145/95 mm Hg in the NRF patients. A maximum decrease of 37/22 mm Hg and 32/19 mm Hg, respectively, was seen within 1.5 hours after dose and at 12 hours the reduction was 12/9 and 15/10 mm Hg, respectively, compared to baseline values. At steady state the morning blood pressure before dose was 152/87 mm Hg in the IRF patients and 129/86 mm Hg in the NRF patients. Similar maximum decreases and effects at 12 hours were seen after dose on day 29 as on day 1. Data on the effect on diastolic blood pressure and plasma felodipine concentrations were well fitted to the Emax model. The maximum reduction in diastolic blood pressure using this model was 27% and the plasma concentration leading to 50% of the maximum effect was 6.2 nmol/L. In conclusion, renal disease does not affect the pharmacokinetics of felodipine. The pharmacokinetic and pharmacodynamic effects of felodipine are not altered during steady state. The renal excretion of inactive metabolites is reduced in IRF. However, the accumulation of metabolites in the blood does not affect the protein binding or the clearance of felodipine. No dosage adjustment of felodipine seems to be necessary in patients with hypertension and renal impairment.

Adult↗
PubMed1989

Effects of felodipine on plasma digoxin levels and haemodynamics in patients with heart failure.

The interaction between felodipine and digoxin was studied after a single oral dose and at steady state in 14 patients with congestive heart failure. Felodipine (10 mg) was randomly given as an extended release (FER) tablet in a double-blind, placebo-controlled, cross-over fashion. In addition, felodipine (10 mg) was given openly as a plain tablet, following the double-blind period. Each period lasted for 7 d. Felodipine ER did not alter the pharmacokinetics of digoxin when given as a single dose or at steady state compared with placebo. At steady state the felodipine plain tablet resulted in an 11% increase (P less than 0.05) in peak plasma concentrations of digoxin. Systolic time intervals as noninvasively measured haemodynamic parameters were not significantly altered following the felodipine ER period, while the felodipine plain tablet significantly decreased the pre-ejection/left ventricular ejection time ratio compared to placebo.

Aged↗