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Vol 9, No 3 (2005)
Prace oryginalne
Published online: 2005-05-11
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Higher efficacy of oral nitrendipine admininstration in comparison with sublingual route. Pharmacokinetic and pharmacodynamic evaluation in hypertensive urgencies

Rafał Dąbrowski, Zygmunt Sadowski, Hanna Goldnik, Dorota Marszałek, Paweł K. Kunicki, Cezary Sosnowski, Ilona Kowalik, Jacek Woźniak, Hanna Szwed
Nadciśnienie tętnicze 2005;9(3):168-177.

open access

Vol 9, No 3 (2005)
Prace oryginalne
Published online: 2005-05-11

Abstract

Background In management of hypertensive urgencies the common opinion exists, that antihypertensive drugs given sublingually are more efficacious than administered orally. The aim of the study was to assess plasma concentrations and effect (blood pressure reduction) after sublingual [SL], oral [PO] and sublingual and oral [SL + PO] administration [adm] of 5 mg nitrendipine [NIT].
Material and methods NIT drops, dose 5 mg, were administered to 12 moderate hypertensive patients with mean initial blood pressure 167/108 (± 9/9) mm Hg, mean age 55 ± 9 years, body mass 81 ± 13 kg. Patients were given NIT randomly in comparison with placebo: sublingually (keeping drops 20 minutes in the mouth and then removing the rest), orally (swallowing drops), and combined (keeping drops in the mouth for 20 min then swallowing). BP was recorded for 24 hrs using ambulatory BP monitoring (SpaceLabs 90207), readings every 10 min. NIT levels were measured in 16 blood samples drawn for 8 hrs after drug intake by HPLC method (sensitivity 2 ng/ml).
Results Highest NIT concentrations were measured after POadm: Cmax 32.8 ± 9 ng/ml (tmax 1.0 h) and after SL + PO: 33.8 ± 8 ng/ml (tmax 0.96 h) vs. SL 15.1 ± 4 ng/ml (tmax 0.53). The concentrations and bioavailability of NIT after 3 ways of administration were compared after 15 min (0.25 h), because latter differences were due to low absorption after SL administration within 20 minutes: 2.81 mg only (56.2% given dose). NIT concentrations after 0.25 h were for PO administration: 14.4 ± 7 ng/ml, SL + PO: 10.1 ± 6.9 ng/ml and SL: 7.3 ± 3.4 ng/ml. Total AUC after PO administration was 90.5 ± 35 ng.h/ml (AUC after 0.25 h: 1.5 ng.h/ml). Total AUC after SL + PO was 60.0 ± 29 ng.h/ml (AUC after 0.25 h: 0.9). And finally: total AUC after SL administration was only 12.8 ± 7 ng.h/ml (after 0.25 h: 1.1). This indicated that absorption from GI tract was faster than from oral mucosa. Systolic blood pressure reductions [SBP] after 0.25 was, respectively, for PO administration: 7.1 mm Hg (p < 0.05), SL + PO: 3.2 mm Hg (ns), and for SL: 5.5 mm Hg (ns). Significant SBP reduction was observed after PO administration for 0.25–10 hrs (max after 3 h, –17.2%), after SL + PO for 1–10 hrs (max after 2.5 h, –14.9%). In all patients 1 h after PO and SL + PO administration > 10% reduction of SBP was registered. After SL no significant reduction of SBP was observed.
Conclusions Study demonstrated the faster absorption of NIT from gastro-intestinal tract than from oral mucosa. Only after PO and SL+PO administration greater and prolonged reduction of SBP was observed. The pure sublingual administration does not exist in practice: only small part of drug is absorbed from oral mucosa and most part of drug after swallowing is absorbed from gastro-intestinal tract.

Abstract

Background In management of hypertensive urgencies the common opinion exists, that antihypertensive drugs given sublingually are more efficacious than administered orally. The aim of the study was to assess plasma concentrations and effect (blood pressure reduction) after sublingual [SL], oral [PO] and sublingual and oral [SL + PO] administration [adm] of 5 mg nitrendipine [NIT].
Material and methods NIT drops, dose 5 mg, were administered to 12 moderate hypertensive patients with mean initial blood pressure 167/108 (± 9/9) mm Hg, mean age 55 ± 9 years, body mass 81 ± 13 kg. Patients were given NIT randomly in comparison with placebo: sublingually (keeping drops 20 minutes in the mouth and then removing the rest), orally (swallowing drops), and combined (keeping drops in the mouth for 20 min then swallowing). BP was recorded for 24 hrs using ambulatory BP monitoring (SpaceLabs 90207), readings every 10 min. NIT levels were measured in 16 blood samples drawn for 8 hrs after drug intake by HPLC method (sensitivity 2 ng/ml).
Results Highest NIT concentrations were measured after POadm: Cmax 32.8 ± 9 ng/ml (tmax 1.0 h) and after SL + PO: 33.8 ± 8 ng/ml (tmax 0.96 h) vs. SL 15.1 ± 4 ng/ml (tmax 0.53). The concentrations and bioavailability of NIT after 3 ways of administration were compared after 15 min (0.25 h), because latter differences were due to low absorption after SL administration within 20 minutes: 2.81 mg only (56.2% given dose). NIT concentrations after 0.25 h were for PO administration: 14.4 ± 7 ng/ml, SL + PO: 10.1 ± 6.9 ng/ml and SL: 7.3 ± 3.4 ng/ml. Total AUC after PO administration was 90.5 ± 35 ng.h/ml (AUC after 0.25 h: 1.5 ng.h/ml). Total AUC after SL + PO was 60.0 ± 29 ng.h/ml (AUC after 0.25 h: 0.9). And finally: total AUC after SL administration was only 12.8 ± 7 ng.h/ml (after 0.25 h: 1.1). This indicated that absorption from GI tract was faster than from oral mucosa. Systolic blood pressure reductions [SBP] after 0.25 was, respectively, for PO administration: 7.1 mm Hg (p < 0.05), SL + PO: 3.2 mm Hg (ns), and for SL: 5.5 mm Hg (ns). Significant SBP reduction was observed after PO administration for 0.25–10 hrs (max after 3 h, –17.2%), after SL + PO for 1–10 hrs (max after 2.5 h, –14.9%). In all patients 1 h after PO and SL + PO administration > 10% reduction of SBP was registered. After SL no significant reduction of SBP was observed.
Conclusions Study demonstrated the faster absorption of NIT from gastro-intestinal tract than from oral mucosa. Only after PO and SL+PO administration greater and prolonged reduction of SBP was observed. The pure sublingual administration does not exist in practice: only small part of drug is absorbed from oral mucosa and most part of drug after swallowing is absorbed from gastro-intestinal tract.
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Keywords

nitrendipine; oral and sublingual; administration; blood pressure reduction

About this article
Title

Higher efficacy of oral nitrendipine admininstration in comparison with sublingual route. Pharmacokinetic and pharmacodynamic evaluation in hypertensive urgencies

Journal

Arterial Hypertension

Issue

Vol 9, No 3 (2005)

Pages

168-177

Published online

2005-05-11

Bibliographic record

Nadciśnienie tętnicze 2005;9(3):168-177.

Keywords

nitrendipine
oral and sublingual
administration
blood pressure reduction

Authors

Rafał Dąbrowski
Zygmunt Sadowski
Hanna Goldnik
Dorota Marszałek
Paweł K. Kunicki
Cezary Sosnowski
Ilona Kowalik
Jacek Woźniak
Hanna Szwed

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