The disposition of the local anaesthetic, pentacaine, in rats and mice

Bezek, S; Ščasnár, V.; Trnovec, T.; Ďurišová, M; Faberová, V.; Beneš, L

doi:10.1002/bdd.2510070205

Cited by 13 publications

(2 citation statements)

References 4 publications

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“…Besides carbisocaine, the pharmacokinetics of two other compounds from the group of basic carbanilates with local anaesthetic activity, pentacaine (13,14) and heptacaine (15), has been studied. The physico-chemical properties (pentacaine, heptacaine, carbisocaine: pK a 8.6, 8.9, 8.8, respectively; partition coefficient in octanol-buffered saline 9000, 5100, 2800, respectively) and the pharrnacokinetic pattern of these substances reveal much similarity.…”

Section: Discussionmentioning

confidence: 99%

“…Carbisocaine quickly disappears from plasma after IV administration and rapidly diffuses into its relatively large volume of distribution. The elimination half-life of plasma carbisocaine 16I.2± 37.5 min is larger than that of pentacaine 99.0 ± 14.I min (13), but shorter than that of heptacaine 228.4 ± 8.9 min (15). The volume of distribution in steady state, Yd ss = 5779 mIlkg, is a sign of high affinity of carbisocaine to peripheral tissues.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of carbisocaine in rats and mice

Bezek

Faberová

Ščasnár

et al. 1988

European Journal of Drug Metabolism and Pharmacokinetics

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[14C]carbisocaine, N-(2-(2-[1-14C]-heptyloxyphenylcarbamoyloxy)-propyl)-diethylammoni um chloride was administered to male Wistar rats, weighing 180-210 g IV in doses of 0.425, 1.425, 2.425 or 4.425 mg/kg or orally in a dose of 2.425 mg/kg. Extraction of carbisocaine from alkaline media into n-heptane was used for assessment of the unchanged drug in plasma, organs and excreta in predetermined time intervals. The two-way analysis of variance confirmed the insignificant effect of subject variability of experimental animals (p greater than 0.05) on plasma data after IV administration. Plasma data following the IV administration were approximated by a linear open two-compartment model with elimination from the central compartment. Regression analysis indicated linearity between carbisocaine plasma AUC and the IV administered dose within the range tested. The following model parameters were obtained: elimination half-life 161.2 +/- 37.5 min, total body clearance 59.5 ml/min/kg, distribution volume in steady state 5616.2 ml/kg and mean residence time 96.7 min. The systemic availability of the orally given carbisocaine was 45.2%, assessed by AUCpo/AUCiv (0-360 min). The brain uptake index of carbisocaine in relation to 3H2O was 57.7 +/- 3.9%. Whole body autoradiographs of mice injected with [14C]carbisocaine documented accumulation of 14C in gall and urinary bladder and in the gut contents and the effective placental barrier against carbisocaine and its metabolites.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of carbisocaine in rats and mice

Bezek

Faberová

Ščasnár

et al. 1988

European Journal of Drug Metabolism and Pharmacokinetics

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Effects of inducers and inhibitors of mixed‐function oxidases on the biliary excretion of pentacaine metabolites

Kukan

Bezek

Ščasnár

et al. 1990

Biopharm & Drug Disp

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The biliary excretion of 3H-pentacaine and its metabolites was studied in rats pretreated with an inducer or inhibitor of mixed-function oxidases. Over one-fourth (25.8 per cent) of a 2 mg kg-1 intraportal dose of 3H-pentacaine was excreted in bile in urethaneanaesthetized control rats within 3 h. The radioactivity appeared in the form of the parent drug, basic metabolites, and metabolite conjugates, 3.1, 86.5, and 10.4 per cent of the total radioactivity excreted, respectively. Pretreatment of rats with phenobarbital enhanced only slightly the biliary excretion of basic metabolites, and pretreatment with 3-methylcholanthrene had no effect. Phenobarbital also increased the initial rate of excretion of conjugates, but this effect was not sustained. 3-Methylcholanthrene had a tendency to impair excretion of conjugates by bile. Pretreatment of rats with SKF 525-A decreased the biliary excretion of both basic metabolites and conjugates while cimetidine did not alter significantly the biliary excretion of pentacaine metabolites. These results suggest that the canalicular transport of metabolites may be the most important factor in controlling pentacaine metabolite excretion in bile.

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Kinetics of biliary elimination of pentacaine in rats

Bezek¹,

Ščasnár²,

Kukan³

et al. 1990

Biopharm & Drug Disp

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Pentacaine, a local anaesthetic of the carbanilate type, administered intravenously as 3H-pentacaine, 2 mg kg-1 to rats, was eliminated in the bile mainly in the form of metabolites (20.5 +/- 1.5 per cent of the dose) and as parent drug (0.1 per cent of the dose) within 3 days. In control rats 32.2 +/- 2.5 and 37.8 +/- 2.5 per cent of 3H-dose, representing pentacaine metabolites, were excreted in the urine and faeces, respectively. In bile-duct-cannulated rats 35.7 +/- 6.8, 11.2 +/- 3.4, and 20.5 +/- 1.5 per cent of 3H-dose were excreted in the urine, faeces, and bile, respectively. The high 3H recovered in faeces in animals with diverted bile flow indicated passage of pentacaine metabolites through the intestinal wall. The excretion of pentacaine and its metabolites in bile was an active process, since the ratio bile/plasma concentration rapidly attained values approaching 10. In rats with ligated ureters the biliary elimination of pentacaine and its metabolites was enhanced, compensating for impaired urinary excretion. This was accompanied by increased plasma and brain levels of 3H compared with untreated controls.

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The disposition of the local anaesthetic, pentacaine, in rats and mice

Cited by 13 publications

References 4 publications

Pharmacokinetics of carbisocaine in rats and mice

Pharmacokinetics of carbisocaine in rats and mice

Effects of inducers and inhibitors of mixed‐function oxidases on the biliary excretion of pentacaine metabolites

Kinetics of biliary elimination of pentacaine in rats

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