Very few studies have been devoted to the influence of the time of the year, i.e. seasonal variations, on drug kinetics. This study aims to evaluate whether or not the kinetics of bupivacaine varied according to the time of the year in mice. Eight groups of 30 animals each received bupivacaine (20 mg/kg i.p.) at a specific month of the year, i.e. February (second week), March (first week), May (fourth week), July (first week), September (fourth week), November (second and third weeks) and December (first week), at the same time of the day (10.00 h). Total bupivacaine serum concentrations were determined by using a specific gas liquid chromatographic method on blood samples collected by decapitation at 0.25, 0.5, 1, 2, 4 and 6 h after drug administration. Pharmacokinetic variables were determined, according to a non linear fitting method (two compartment open model). All data were compared by ANOVA and the influence of the month of the year was estimated by Cosinor analysis. According to the month of the year, the kinetic parameters were significantly different except for Vd: the maximal Cmax occurred in July, the highest Tmax occurred in May, the maximal T1/2β and the maximal AUC were observed in February. The mechanisms underlying these variations may depend on seasonal variations of resorption, distribution, metabolism and elimination.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Lemmer B. (1981): Chronopharmacokinetics. In: Breimer D., Speiser P. (Eds): Topics in Pharmaceutical Sciences. Amsterdam, Elsevier, North Holland Biomedical Press, pp. 49–68.
Reinberg A., Smolensky M.H. (1982): Circadian changes of drug disposition in man. Clin. Pharmacokinet., 7, 401–420.
Bruguerolle B. (1987): Données récentes en chronopharmacocinétique. Pathol. Biol., 35, 925–934.
Reinberg A., Levi F., Smolensky M., Labrecque G., Ollagnier M., Decousus H., Bruguerolle B. (1990): Chronokinetics. In: Hansch C. (Ed.) Comprehensive Medicinal Chemistry, vol 5. oxford, Pergamon, pp. 279–296.
Bruguerolle B., Lemmer B. (1993): Recent advances in chronopharmacokinetics — methodological problems. Life Sci., 52, 1809–1824.
Lemmer B., Bruguerolle B. (1994): Chronopharmacokinetics. Are they clinically relevant? Clin. Pharmacokinet., 26, 419–427.
Bruguerolle B., Emperaire N. (1991): Flumazenil and bupivacaine-induced toxicity: inverse agonist type activity. Life Sci., 49, 185–188.
Bruguerolle B., Emperaire N. (1992): Local anaesthetics-induced toxicity may be modified by low doses of flumazenil. Life Sci., 50, 185–187.
Bruguerolle B., Lorec A.M. (1993): Lack of bupivacaine kinetic changes induced by flumazenil in mice. Life Sci., 52, 165–167.
Bruguerolle B. (1993): Effects of calcium channel blockers on bupivacaine-induced toxicity. Life Sci., 53, 349–353.
Bruguerolle B., Loree A.M. (1994): Bupivacaine kinetic changes induced by diltiazem in mice. Life Sci., 54, 315–319.
Bjork M., Petterson K.J., Osterlof G. (1990): Capillary gas chromatographic method for the simultaneous determination of local anesthetics in plasma samples. J. Chromatogr., 533, 229–234.
Lorec A.M., Bruguerolle B., Attolini L., Roucoules X. (1994): Rapid simultaneous determination of lidocaine, bupivacaine and their two main metabolites using capillary gas liquid chromatography with nitrogen phosphorus detector. Ther. Drug Monit., 16, 592–595.
Lu D.R., Mao F. (1993): An interactive program for pharmacokinetic modeling. J. Pharm. Sci., 82, 537–542.
Nelson W., Tong Y.L., Lee Y.K., Halberg F. (1979): Methods for cosinor rhythmometry. Chronobiologia, 6, 305–323.
Bruguerolle B., Prat M. (1987): Temporal changes in bupivacaine kinetics. J. Pharm. Pharmacol., 39, 148–149.
Pericin C. (1971): Effect of seasonal variation of the acute toxicity of cyclophosphamide in the Chinese hamster (Cricetelus griseus) and the mouse under laboratory conditions. Experientia, 37, 401–402.
Bruguerolle B., Prat M., Douylliez C., Dorfman P. (1988): Are there circadian and circannual variations in acute toxicity of phenobarbital in mice? Fundam. Clin. Pharmacol., 2, 301–304.
Belanger P.M., Dore F., Labrecque G. (1984): Monthly variations in the clearance of antipyrine in the rat. Res. Commun. Chem. Pathol. Pharmacol., 46, 53–66.
Reinberg A., Schuller E., Deslanerie N., Clench J., Helary M. (1977): Rythmes circadiens et circannuels des leucocytes, proteines totales, immunoglobulines A, G et M. Etude chez neuf adultes jeunes et sains. Nouv. Presse Med., 6, 3819–3823.
Tucker G.T., Mather L.E. (1979): Clinical pharmacokinetics of local anaesthetics. Clin. Pharmacokinet., 4, 241–278.
Wolfe G.W., Schnell R.C. (1979): Annual difference in daily variations in hepatic drug metabolizing enzyme activity and plasma hormone levels in the rat. Pharmacology, 19, 116–120.
Cal J., Dorian C., Catroux P., Pariat C., Cambar J. (1989): Les facteurs saisonniers comme source d’erreur en toxicologie expérimentale. Sci. Tech. Anim. Lab., 14, 121–127.
About this article
Cite this article
Attolini, L., Gantenbein, M., Lorec, A.M. et al. Seasonal variations in the kinetics of bupivacaine in the mouse. European Journal of Drug Metabolism and Pharmacokinetics 21, 257–260 (1996). https://doi.org/10.1007/BF03189723
- Seasonal variation