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Effect of dehydration and hyperosmolal hydration on lignocaine and metabolites disposition in conscious rabbits
Author(s) -
Chamelian M.,
Lécrivain A.,
Robichaud A.,
Souich P.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb16211.x
Subject(s) - vasopressin , chemistry , dehydration , medicine , endocrinology , osmole , atrial natriuretic peptide , plasma levels , biochemistry
1 The present study aimed to investigate the effect of dehydration and hyperosmolal hydration on the disposition of lignocaine and two of its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX). 2 Lignocaine was infused to three groups of conscious rabbits: controls, rabbits previously deprived of water for 48 h and rabbits receiving an infusion of 2.5% NaCl. 3 In dehydrated and hyperosmolal‐hydrated rabbits, plasma osmolality was 321 ± 1 and 313 ± 1 mOsm kg −1 , respectively ( P <0.01 compared to controls, 285 ± 1 mOsm kg −1 ). In dehydrated animals, baseline values of plasma arginine vasopressin (AVP) concentrations and plasma renin activity (PRA) were higher than in controls, i.e. 12.4 ± 1.4 pg ml −1 and 15.4 ± 1.7 ng AI ml −1 h −1 vs. 3.4 ± 0.2 pg ml −1 ( P <0.01), and 5.1 ± 0.6 ng AI ml −1 h −1 ( P <0.01), respectively; atrial natriuretic peptide (ANP) decreased from 55 ± 11 to 32 ± 4 pg ml −1 ( P <0.05). Compared to controls, hyperosmolal hydration only increased AVP to 15.5 ± 0.7 pg ml −1 ( P <0.01). 4 Under both experimental conditions, lignocaine plasma concentrations were almost double ( P <0.01) those in controls, due to a lower systemic clearance, e.g. 54 ± 3 and 59 ± 1 vs. 96 ± 5 ml min −1 kg −1 , respectively. Plasma levels of MEGX increased ( P <0.01) only in dehydrated animals, although GX plasma concentrations were augmented ( P <0.01) about three fold in both groups of animals. The changes in lignocaine plasma concentrations were correlated with AVP levels ( R 2 = 0.5168, P <0.001). 5 To document the effect of AVP on hepatic plasma flow, another group of rabbits received on separate occasions two doses of AVP (17 and 84 ng kg −1 ) while receiving an infusion of indocyanine green. AVP reduced hepatic plasma flow from 38.9 ± 2.7 ml min −1 to 19.6 ± 2.5 ml min −1 ( P <0.01). The predicted maximal AVP‐induced decrease in hepatic plasma flow was 19.6 ml min −1 kg −1 ( E max ), and AVP concentration eliciting 50% of E max (ED 50 ) was 28.7 pg ml −1 . 6 It is concluded that both dehydration and hyperosmolal hydration alter the disposition of lignocaine and two of its metabolites.