The effect of nisoldipine on apparent liver blood flow and effective renal plasma flow.

1 The pharmacokinetics and haemodynamic effects of nisoldipine on long term i.v. infusion of 2.40 mg and 9.59 mg in 25 h were studied in six healthy subjects. Liver blood flow at 0.8 and 24 h was assessed by measuring indocyanine green (ICG) clearance.2 After high-dose nisoldipine, systemic clearance was 0.99 ± 0.16 1 min-', volume of distribution was 5.8 ± 1.5 1 kg-' and elimination half-life was 10.7 ± 2.4 h. The pharmacokinetic parameters were similar after low-dose nisoldipine. 3 No significant changes in apparent liver blood flow were observed after either highdose or low-dose nisoldipine. 4 Systolic blood pressure did not change, whereas diastolic blood pressure decreased by approximately 10% during both treatments. Maximal increase in heart rate was approximately 37% at high-dose infusion, whereas this was one half lower during the low-dose regimen. 5 Increased infusion rate results in an unfavourable shift in the haemodynamic effect profile of nisoldipine.

Section: Introductionmentioning

confidence: 99%

The influence of infusion rate on the pharmacokinetics and haemodynamic effects of nisoldipine in man.

Harten¹,

Brummelen²,

Zeegers³

et al. 1988

“…The influence of liver blood flow on absorption kinetics has been described for other dihydropyridines. Nisoldipine increases liver blood flow only after oral administration during the absorption phase, but not after intravenous administration (Meredith et al, 1985;van Harten et al, 1989). The observations in studies with nifedipine (Feely, 1984;Kleinbloesem et al, 1984) also demonstrate the importance of liver blood flow with respect to absorption kinetics.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of felodipine after intravenous and chronic oral administration in patients with congestive heart failure.

Dunselman

Edgar

Scaf

et al. 1989

1 In a randomized, parallel, double-blind study felodipine was administered to 11 and placebo to 12 patients with congestive heart failure. The kinetics of felodipine were studied after acute intravenous administration and after chronic oral treatment for 8 weeks. The relationship between cardiac output and pharmacokinetics was analyzed. The pharmacokinetic data were compared with data from young healthy individuals and hypertensive patients.2 After oral therapy, significant correlations were found between cardiac output and AUC and systemic bioavailability (F). Furthermore, cardiac output before therapy was also significantly correlated with absorption characteristics. No relationship could be demonstrated between cardiac output and i.v. pharmacokinetics. A comparison of patients with heart failure and young healthy individuals revealed that the AUC was three times higher in heart failure patients, while V55 and the ratio of the AUC of the pyridine metabolite to that of felodipine were similar. Oral clearance was reduced by 50% and the terminal half-life was concomitantly increased. Pharmacokinetic data for felodipine are similar in patients with heart failure to published data from elderly hypertensive patients. 3 An increase in liver blood flow during chronic oral therapy, induced by felodipine itself, appears to explain an increase in bioavailability and thus to higher plasma drug concentrations. Thus, it is advisable to start felodipine treatment at a low dosage in patients with congestive heart failure.

“…Hepatic blood flow was assessed 1 h after drug administration following the separate intravenous injection of indocyanine green and by subsequent measurement of its clearance (assuming complete hepatic extraction) from venous blood samples obtained at 3 min intervals for 21 min (Meredith et al, 1985). Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were also determined 1 h after drug administration from the clearance of radio pharmaceuticals, as previously described (Meredith et al, 1985).…”

Section: Dmentioning

confidence: 99%

“…There is evidence in both conditions (Aoki et al, 1978;Dargie et al, 1981;De Caprio et al, 1990;Ekelund & Oro, 1979;Yagil et al, 1983) to suggest that the therapeutic results of such combinations are at least additive but it is not clear whether this only reflects a summation of their pharmacological activities or whether there is also an underlying pharmacokinetic interaction leading to a beneficial alteration in the plasma concentrations of one or other drug. There is evidence that dihydropyridine calcium antagonist drugs, including nisoldipine, as a result of their vasodilator activity, are able to modify splanchnic, hepatic and renal blood flow (Feely, 1984;Meredith et al, 1985) and this affords them the potential to interfere with the disposition and elimination of concurrently administered drugs.…”

Section: Introductionmentioning

confidence: 99%

The interactions between nisoldipine and two beta‐adrenoceptor antagonists‐atenolol and propranolol.

Elliott

Modesti

McNally

et al. 1991

Self Cite

1. The interactions between the dihydropyridine calcium antagonist nisoldipine and two beta‐adrenoceptor blocker drugs (atenolol and propranolol) were investigated in two groups of healthy normotensive subjects. 2. The steady state plasma concentrations of both beta‐ adrenoceptor blockers were significantly altered by the addition of nisoldipine: for propranolol there were significant increases in Cmax, by about 50%, and in AUC by about 30% and for atenolol there was a significant increase in Cmax, by about 20%. 3. The addition of nisoldipine was also associated with significant changes in apparent liver blood flow (measured by indocyanine green clearance) from 1.4 to 2.4 l min‐1 in the atenolol group and from 1.3 to 2.3 l min‐1 in the propranolol group. 4. Both nisoldipine‐beta‐adrenoceptor blocker combinations were associated with small enhanced blood pressure reductions e.g. from 104/60 with atenolol alone to 98/50 mm Hg with the combination but there was no alteration to the extent of beta‐ adrenoceptor blockade (as assessed by bicycle ergometry). 5. This pharmacodynamic profile in healthy normotensives is consistent with the known therapeutic efficacy of such combination treatments in patients with hypertension and angina. 6. It is suggested that there is a pharmacokinetic component to the efficacy of this type of combination, perhaps reflecting vasodilator‐induced changes in drug absorption and/or hepatic extraction.