Artículos de revistas
Drug-delivery Systems For Racemic Bupivacaine (s50-r50) And Bupivacaine Enantiomeric Mixture (s75-r25): Cyclodextrins Complexation Effects On Sciatic Nerve Blockade In Mice [sistemas De Liberação Controlada Com Bupivacaína Racêmica (s50-r50) E Mistura Enantiomérica De Bupivacaína (s75-r25): Efeitos Da Complexaćão Com Ciclodextrinas No Bloqueio Do Nervo Ciático Em Camundongos]
Registro en:
Revista Brasileira De Anestesiologia. , v. 55, n. 3, p. 316 - 328, 2005.
347094
2-s2.0-18844461924
Autor
Ribeiro De Araujo D.
Fernandes Fraceto L.
De Assuncao Braga A.D.F.
De Paula E.
Institución
Resumen
BACKGROUND AND OBJECTIVES: Bupivacaine-induced side effects have led to the search for new local anesthetics (LA) with similar potency and lower toxicity, such as bupivacaine enantiomeric mixture (S75-R25). Drug-delivery systems for LA in carriers, such as cyclodextrins (CD), have been developed to improve anesthetic potency and therapeutic index of those drugs. This study aimed at preparing, characterizing and evaluating the anesthetic efficacy of inclusion complexes of bupivacaine enantiomeric mixture (S75-R25) and racemic bupivacaine (S50-R50) with hydroxypropylβ- cyclodextrin (HPβ-CD) comparing them to clinically available preparations. METHODS: Inclusion complexes were obtained by mixing appropriate volumes of HPβ-CD and S50-R50 or S75-R25 to final 1:1 or 1:2 molar ratios and were characterized by phase solubility experiments. Affinity constants (K) were determined between HPβ-CO and each LA. Motor and sensory blocks induced by plain or complexed LA formulations were evaluated in mice by sciatic nerve block. Three LA concentrations were used during the experiment: 0.125, 0.25 and 0.5%. RESULTS: Solubility experiments results were indicative of S50-R50:HPβ-CD and S75-R25:HPβ-CD complexation, with similar affinity constant (K) values: 14.7 M -1 and 14.3 M -1, respectively. In vivo experiments have shown that complexation has enhanced differential nerve blockade induced by LA: i) motor blockade duration induced by S75-R25 was similar, to the induced by but less intense S50-R50 (p < 0.001). S50-R50 HPβ-CD and S75-R25 HPβ-CD complexes have decreased onset (p < 0.01 and p < 0.05. respectively), without changing motor block intensity (E max) as compared to plain drugs; ii) sensory block evaluation has revealed higher analgesic intensity with S50-R50 HPβ-CD (2-fold, p < 0.001) and S75-R25 HPβ-CD (1.5-1.8-fold, p < 0.01 and p < 0.001, respectively) with both molar ratios (1:1 and 1:2, LA:CD), in addition to prolonging analgesic effect as compared to S50-R50 and S75-R25. CONCLUSIONS: More pronounced analgesic effects obtained by complexation with HPβ-CD have shown that both formulations. S50-R50 HPβ-CD, are S75-R25 HPβ-CD, are very useful for postoperative pain relief, requiring lower LA concentrations. Nevertheless, it is worth noticing that S75-R25 - being less toxic than racemic bupivacaine - is an interesting alternative for the development of more effective and safe drug-delivery systems as compared to racemic bupivacaine (S50-R50). © Sociedade Brasileira de Anestesiologia, 2005. 55 3 316 328 Mather, L.E., Chang, D.H., Cardiotoxicity with modern local anesthetics: Is there a safer choice? (2001) Drugs, 61, pp. 333-342 Ohmura, S., Kawada, M., Ohta, T., Systemic toxicity and resuscitation in bupivacaine, levobupivacaine, or ropivacaine-infused rats (2001) Anesth Analg, 93, pp. 743-748 Santos, A.C., Dearmas, P.I., Systemic toxicity of levobupivacaine, bupivacaine and ropivacaine during continuous intravenous infusion to nonpregnant and pregnant ewes (2001) Anesthesiology, 95, pp. 1256-1264 Whiteside, J.B., Wildsmith, J.A., Developments in local anesthesia drugs (2001) Br J Anaesth, 87, pp. 27-35 Simonetti, M.P.B., Batista, R.A., Ferreira, F.M.C., Estereoisomeria: A interface da tecnologia industrial de medicamentos e da racionalização terapêutica (1998) Rev Bras Anestesiol, 48, pp. 390-399 Araujo, D.R., Pinto, L.M.A., Braga, A.F.A., Formulações de anestésicos locais de liberação controlada: Aplicações terapêuticas (2003) Rev Bras Anestesiol, 53, pp. 663-671 Szejtli, J., Medicinal applications of cyclodextrins (1994) Med Res Rev, 14, pp. 353-386 Freville, J.C., Dollo, G., Le Corre, P., Controlled systemic absorption and increased anesthetic effect of bupivacaine following epidural administration of bupivacaine-hydroxypropyl-beta- cyclodextrin complex (1996) Pharm Res, 13, pp. 1576-1580 Dollo, G., Thompson, D.O., Le Corre, P., Inclusion complexation of amide-type local anesthetics with β-cyclodextrin and derivates. III. Biopharmaceutics of bupivacaine-SBE7- β-CD complex following percutaneous sciatic nerve administration in rabbits (1998) Int J Pharm, 164, pp. 11-19 Dollo, G., Le Corre, P., Freville, J.C., Biopharmaceutics of local anesthetic-cyclodextrin complexes following loco-regional administration (2000) Ann Pharm Fr, 58, pp. 425-432 Estebe, J.P., Ecoffey, C., Dollo, G., Bupivacaine pharmacokinetics and motor blockade following epidural administration of the bupivacaine- sulphobutylether -7-beta-cyclodextrin complex in sheep (2002) Eur J Anaesthesiol, 19, pp. 308-310 Higuchi, T., Connors, K.A., Phase-solubility techniques (1965) Adv Anal Chem Instr, 4, pp. 117-212 De Paula, E., Schreier, S., Use of a novel method for determination of partition coefficients to compare the effect of local anesthetics on membrane structure (1995) Biochim Biophys Acta, 1240, pp. 25-33 Leszczynska, K., Kau, S.T., A sciatic nerve blockade method to differentiate drug-induced local anesthesia from neuromuscular blockade in mice (1992) J Pharmacol Toxicol Methods, 27, pp. 85-93 Gantenbein, M., Abat, C., Attolini, L., Ketamine effects on bupivacaine local anaesthetic activity and pharmacokinetics of bupivacaine in mice (1997) Life Sci, 61, pp. 2027-2033 Randall, L.O., Selitto, J.J., A method for measurement of analgesic activity of inflamed tissue (1957) Arch Int Pharmacodyn, 11, pp. 409-419 De Araujo, D.R., Cereda, C.M., Brunetto, G.B., Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice (2004) Can J Anaesth, 51, pp. 566-572 Zar, J.H., (1996) Biostatistical Analysis, 3 rd Ed., pp. 180-216. , New Jersey, Prentice-Hall Dollo, G., Le Corre, P., Chevanne, F., Inclusion complexation of amide-type local anesthetics with β-cyclodextrin and derivates. II. Evaluation of affinity constants and in vitro transfer rate constants (1996) Int J Pharm, 136, pp. 165-174 Simonetti, M.P.B., Valinetti, E.A., Ferreira, F.M., Avaliação da atividade anestésica local da S(-) bupivacaína: Estudo experimental in vivo em nervo ciático de rato (1997) Rev Bras Anestesiol, 47, pp. 425-434 Sinnott, C.J., Strichartz, G.R., Levobupivacaine versus ropivacaine for sciatic nerve block in the rat (2003) Reg Anesth Pain Med, 28, pp. 294-303 Tanaka, P.P., Souza, R.O., Salvalaggio, M.F.O., Estudo comparativo entre a bupivacaína a 0.5% e a mistura enantiomérica de bupivacaína (S75-R25) a 0.5% em anestesia peridural em pacientes submetidos a cirurgia ortopédica de membros inferiores (2003) Rev Bras Anestesiol, 53, pp. 331-337 Cortes, C.A.F., Oliveira, A.S., Castro, L.F.L., Estudo comparative entre bupivacaína a 0.5%, mistura enantiomérica de bupivacaína (S75-R25) a 0.5% e ropivacaína a 0.75% associadas ao fentanil em anestesia peridural para cesarianas (2003) Rev Bras Anestesiol, 53, pp. 177-187 Gonçalves, R.F., Lauretti, G.R., Mattos, A.L., Estudo comparative entre bupivacaína a 0.5% e mistura enantiomérica de bupivacaína (S75-R25) a 0.5% em anestesia peridural (2003) Rev Bras Anestesiol, 53, pp. 169-176