Ranitidine increases the bioavailability of nitrendipine in patients with arterial hypertension.

1. In a randomized placebo-controlled study, 12 hypertensive patients were treated po for one week with 20 mg nitrendipine once daily plus placebo, twice daily and later with the same dose of nitrendipine plus 300 mg ranitidine (150 mg twice a day). 2. When ranitidine was coadministered, plasma nitrendipine levels (0-24 h) were significantly increased (P < 0.001), although no significant increase in peak plasma nitrendipine level (Cmax) was observed due to the wide range of variation of this parameter (Cmax) in hypertensive patients. 3. Ranitidine coadministration increased the area under the curve for 24-h (AUC0-24) plasma concentration vs time, from 49.07 +/- 6.28 micrograms.h/l to 82.35 +/- 2.57 micrograms.h/l (P < 0.01). This significant increase caused a reduction in total body clearance from 2008.33 +/- 246.33 to 1284.00 +/- 182.16 ml/min (P < 0.002). 4. Nitrendipine bioavailability was increased by 89% when ranitidine was coadministered but the kinetic effect of this drug interaction is unlikely to be of clinical relevance since no adverse effects were observed in patients evaluated after ranitidine association.

Farmacocinetica da nitrendipina em pacientes com hipertensao arterial: estudo de interacao / Pharmacokinetics of nitrendipine in patients with arterial hypertension: a drug interaction study

Em estudo randomizado cruzado administrou-se nitrendipina, sob forma de comprimidos, 20mg/dia p.o. e placedo, ou dose identica de nitrendipina associada a 300 mg de ranitidina, 150 mg duas vezes ao dia a 12 pacientes com hipertensao essencial sistemica. Um deles foi excluido do estudo apos desenvolvimento de falha renal. Os niveis plasmaticos da nitrendipina no intervalo de dose foram significativamente aumentados, p < 0,001, quando a ranitidina foi associada. O clearance da antipirina foi reduzido em 15%, p < 0,001, pela ranitidina numa extensao inferior aquela provocada pela cimetidina. A depuracao plasmatica foi reduzida de 2008 mais ou menos 246ml/min para 1284 mais ou menos 182 ml/min, p < 0,002, ranitidina; consequentemente o parametro AUC 0-24 foi aumentado, p < igual 0,01, quando a ranitidina foi coadministrada. Os parametros cineticos da nitrendipina estimados nao foram significativamente alterados pela ranitidina, relativamente as constantes de velocidade e respectivas meias-vidas das fases de absorcao, distribuicao e eliminacao. Nao ha evidencia de acumulo da nitrendipina pela ranitidina, apesar da interacao farmacocinetica obtida em pacientes hipertensivos

Antihypertensive effect and pharmacokinetics of nitrendipine in children.

Nitrendipine, a new calcium-channel antagonist, was used to treat 25 children (aged 6 months to 17 years) with severe hypertension. Systolic and diastolic blood pressures (mean +/- SEM) fell from 148 +/- 2/99 +/- 2 mm Hg to 128 +/- 4/77 +/- 3 mm Hg after 24 hours and to 121 +/- 2/75 +/- 2 mm Hg after 2 weeks. No further reductions in systolic or diastolic blood pressure were observed after continued therapy. Transient reflex tachycardia occurred during the first week of therapy. Other adverse effects were uncommon and included headaches, flushing, palpitations, and edema. Pharmacokinetic parameters were estimated at steady state after an oral dose of 0.56 +/- 0.04 mg/kg in 13 children. Although absolute oral bioavailability could not be determined, estimates of the area under the plasma concentration versus time curve, the apparent peak serum concentration, and the apparent time at which the peak serum concentration occurred indicated that both the rate of absorption and oral bioavailability are variable. Coadministration of nitrendipine with food decreased the rate of absorption and may have reduced oral bioavailability. A relationship between age and the apparent plasma elimination half-life of nitrendipine was not observed. Nitrendipine, 0.25 to 0.5 mg/kg per dose administered orally every 6 to 12 hours, appeared to be an effective and safe treatment for resistant hypertension in infants and children.