@2024 Afarand., IRAN
ISSN: 2252-0805 The Horizon of Medical Sciences 2013;19(2):71-76
ISSN: 2252-0805 The Horizon of Medical Sciences 2013;19(2):71-76
Effect of Verapamil on Ivermectin Concentration of Dog Serum and Cerebro-spinal Fluid
ARTICLE INFO
Article Type
Original ResearchAuthors
Najafzadeh H. (*)Avizeh R. (1)
Kavousi N. (2)
(*) Department of Pharmacology & Toxicology, Faculty of Veterinary Medicine, Shahid-Chamran University, Ahvaz, Iran
(1) Department of Clinical Pathology, Faculty of Veterinary Medicine, Shahid-Chamran University, Ahvaz, Iran
(2) Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid-Chamran University, Ahvaz, Iran
Correspondence
Address: Department of Pharmacology, Faculty of Veterinary Medicine, Shahid-Chamran University, Golestan Boulevard, Ahvaz, Iran.Phone: +986113330073
Fax: +986113336087
najafzadeh@scu.ac.ir
Article History
Received: August 16, 2012Accepted: June 18, 2013
ePublished: June 25, 2013
ABSTRACT
Aims
Regarding to importance of Ivermectin as a clinical anti-parasite drug, identification of its interaction with other drugs is necessary. At present study, the interaction of Verapamil as an inhibitor P-glycoprotein was evaluated on Ivermectin concentration in serum and cerebrospinal fluid in dog.
Materials & Methods In this experimental study with animal model which was done in faculty of veterinary medicine of Ahvaz in 2011; 10 mixed breed dogs was randomly divided into 2 groups (5 dogs at each group). First group received 0.2mg/kg of Ivermectin for each kilo of body weight and second group received of 3mg/kg of Ivermectin for each kilo of body weight along with verapamil. The level of Ivermectin was detected by HPLC in blood samples 1, 2 and 3 hours and in cerebrospinal fluid 1.5 hours after injection. Statistical analysis was carried out by SPSS 16. Repeated measurement and T-independent test were used for comparison of sample means.
Findings In both groups, the serum concentration of Ivermectin was decreased at second hour and then increased in comparing with first hour. The Ivermectin was not detected cerebrospinal fluid of first group while it was 45.44± 10.91ng/ml in second group.
Conclusion Serum concentration of Ivermectin increases by intramuscular injection after one hour and Verapamil increases cerebraospinal fluid concentration of Ivermectin.
Materials & Methods In this experimental study with animal model which was done in faculty of veterinary medicine of Ahvaz in 2011; 10 mixed breed dogs was randomly divided into 2 groups (5 dogs at each group). First group received 0.2mg/kg of Ivermectin for each kilo of body weight and second group received of 3mg/kg of Ivermectin for each kilo of body weight along with verapamil. The level of Ivermectin was detected by HPLC in blood samples 1, 2 and 3 hours and in cerebrospinal fluid 1.5 hours after injection. Statistical analysis was carried out by SPSS 16. Repeated measurement and T-independent test were used for comparison of sample means.
Findings In both groups, the serum concentration of Ivermectin was decreased at second hour and then increased in comparing with first hour. The Ivermectin was not detected cerebrospinal fluid of first group while it was 45.44± 10.91ng/ml in second group.
Conclusion Serum concentration of Ivermectin increases by intramuscular injection after one hour and Verapamil increases cerebraospinal fluid concentration of Ivermectin.
CITATION LINKS
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[22]Bansal T, Mishra G, Jaggi M, khar RK, Talegaokar S. Effect of P-glycoprotein inhibitor, verapamil, on oral bioavailability and pharmacokinetics of irinotecan in rats. Eur J Pharm Sci. 2009;36(4-5):580-90.
[23] Lemma Gl, Wong Z, Hamman MA, Zaherr NA, Groski JC, Hall SD. The effect of short- and long-term administration of verapamil on the disposition of cytochrome p4503 A and P-glycoprotein substrates. Clin Pharmacol Ther. 2006;79(3):218-30.
[24] Marier JF, Deschenes JL, Hage A, Seliniotakis E, Gritsas A, Flarakos T, et al. Enhancing the uptake of dextromethorphan in the CNS of rats by concomitant administration of the P-gP inhibitor verapamil. Life Sci. 2005;77(23):2911-26.
[25] Neuhaus W, Stessl M, Strizsik E, Bennani-Baiti B, Wirth M, Stefan Toegel S, et al. Blood-brain barrier cell line PBMEC/C1-2 possesses functionally active P-glycoprotein. Neurosci Lett. 2010;469(2):224-8.
[26] Ballent M, Lifschitz A, Virkel G, Mate L, Lanusse C. Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition. J Vet Pharmacol Ther. 2010;33(3):252-9.
[27] Bates N, Chatterton J, Robbins C, Wells K, Hughes J, Stone M, Campbell A. Lipid infusion in the management of poisoning: A report of 6 canine cases. Vet Rec. 2013;172(13):339.
[28] Merola VM, Eubig PA. Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of Pglycoprotein in dogs and cats. Vet Clin North Am Small Anim Pract. 2012;42(2):313-33.
[29] Conen S, Theunissen EL, Vermeeren A, van Ruitenbeek P, Stiers P, Mehta MA, et al. The role of P-glycoprotein in CNS antihistamine effects. Psychopharmacology (Berl). 2013. [Epub ahead of print]
[2] Mealey KL. Canine ABCB1 and macrocyclic lactones: Heartworm prevention and pharmacogenetics. Vet Parasitol. 2008;158(3):215-22.
[3] Bissonnette S, Paradis M, Daneau I, Silversides DW. The ABCB1-1 Delta mutation is not responsible for subchronic neurotoxicity seen in dogs of non-collie breeds following macrocyclic lactone treatment for generalized demodicosis. Vet Dermatol. 2009;20(1):60-6.
[4] Warrington Jill S, Greenblatt DJ, von Moltke L. The effect of age on p-glycoprotein expression and function in the Fischer-344 rat. J Pharmacol Exp Ther. 2004;309(2):730-6.
[5] Ambudkar SV, Kimchi-Sarfaty C, Suna ZE, Gottesman M. P-glycoprotein: From genomics to mechanism. Oncogene. 2003;22(47):7468-85.
[6] Fardel O, Lecureur V, Loyer P, Guillouzo A. Rifampicin enhances anti-cancer drug accumulation and activity in multidrug-resistant cells. Biochem Pharmacol. 1995;49(9):1255-60.
[7] El-Ashmawy IM, El-Nahas AF, Bayad AE. Teratogenic and cytogenetic effects of ivermectin and its interaction with P-glycoprotein inhibitor. Res Vet Sci. 2011;90(1):116-23.
[8] El-Nahas AF, El-Ashmawy IM. Effect of ivermectin on male fertility and its interaction with P-glycoprotein inhibitor (verapamil) in rats. Environ Toxicol Pharmacol. 2008;26(2):206-11.
[9] Gokbulut C, Karademir U, Boyacioglu M, McKellar QA. Comparative plasma dispositions of ivermectin and doramectin following subcutaneous and oral administration in dogs. Vet Parasitol. 2006;135(3-4):347-54.
[10] Prieto JG, Merino G, Pulido MM, Estevez E, Molina AJ, Vila AL, et al. Improved LC method to determine ivermectin in plasma. J Pharmaceut Biomed Anal. 2003;31(4):639-45.
[11] Bartels AL, Kortekaas R, Bart J, Willemsen A, Klerk OL, Vries J, et al. Blood-brain barrier P-glycoprotein function decreases in specific brain regions with aging: A possible role in progressive neurodegeneration. Neurobiol Aging. 2008;30(11):1818-24.
[12] Hendrikse NH, Bart J, de Vries EG, Groen HJ, van der Graaf WT, Vaalburg W. P-glycoprotein at the blood- brain barrier and analysis of drug transport with positron-emissien tomography. J Clin Pharmacol. 2001;1:48-54.
[13] Hopper K, Aldrich J, Haskins SC. Ivermectin toxicity in 17 collies. J Vet Inter Med. 2002;16(1):89-94.
[14] Lespine A, Dupuy J, Alvinerie M, Comera C, Nagy T, Krajcsi P, et al. Interaction of macrocyclic lactones with the multidrug transporters: The bases of the pharmacokinetics of lipid-like drugs. Curr Drug Metabol. 2009;10(3):272-88.
[15] El-Tahtawy A, Glue P, Andrews EN, Mardekian J, Amsden GW, Knirsch CA. The effect of azithromycin on ivermectin pharmacokinetics: A population pharmacokinetic model analysis. PLoS Negl Trop Dis. 2008;2(5):236.
[16] Gonzalez Canga A, Sahagun Prieto AM, Jose Diez Liebana M, Martinez NF, Vega MS, Vieitez JJ. The pharmacokinetics and metabolism of ivermectin in domestic animal species. Vet J. 2009;179(1):25-37.
[17] Eraslan G, Kanbur M, Liman BC, Cam Y, Karabacak M, Altinordulu S. Comparative pharmacokinetics of some injectable preparations containing ivermectin in dogs. Food Chem Toxicol. 2010;48(8-9):2181-5.
[18] Mealey KL, Meurs KM. Breed distribution of the ABCB1-1Delta (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping. J Am Vet Med Assoc. 2008;233(6):921-4.
[19] Han JI, Son HW, Park SC, Na KJ. Novel insertion mutation of ABCB1 gene in an ivermectin-sensitive Border Collie. J Vet Sci. 2010;11(4):341-4.
[20] Wang JC, Liub XY, Lu WL, Chang A, Zhang Q, Goh BC, et al. Pharmacokinetics of intravenously administered stealth liposomal doxorubicin modulated with verapamil in rats. Eur J Pharm Biopharm. 2008;62(1):44-51.
[21] Mankhetkorn S, Teodori E, Garnier-Suillerot A. Partial inhibition of the P-glycoprotein-mediated transport of anthracyclines in viable resistant K562 cells after irradiation in the presence of a verapamil analogue. Chem Biol Int. 1999;121:125-40.
[22]Bansal T, Mishra G, Jaggi M, khar RK, Talegaokar S. Effect of P-glycoprotein inhibitor, verapamil, on oral bioavailability and pharmacokinetics of irinotecan in rats. Eur J Pharm Sci. 2009;36(4-5):580-90.
[23] Lemma Gl, Wong Z, Hamman MA, Zaherr NA, Groski JC, Hall SD. The effect of short- and long-term administration of verapamil on the disposition of cytochrome p4503 A and P-glycoprotein substrates. Clin Pharmacol Ther. 2006;79(3):218-30.
[24] Marier JF, Deschenes JL, Hage A, Seliniotakis E, Gritsas A, Flarakos T, et al. Enhancing the uptake of dextromethorphan in the CNS of rats by concomitant administration of the P-gP inhibitor verapamil. Life Sci. 2005;77(23):2911-26.
[25] Neuhaus W, Stessl M, Strizsik E, Bennani-Baiti B, Wirth M, Stefan Toegel S, et al. Blood-brain barrier cell line PBMEC/C1-2 possesses functionally active P-glycoprotein. Neurosci Lett. 2010;469(2):224-8.
[26] Ballent M, Lifschitz A, Virkel G, Mate L, Lanusse C. Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition. J Vet Pharmacol Ther. 2010;33(3):252-9.
[27] Bates N, Chatterton J, Robbins C, Wells K, Hughes J, Stone M, Campbell A. Lipid infusion in the management of poisoning: A report of 6 canine cases. Vet Rec. 2013;172(13):339.
[28] Merola VM, Eubig PA. Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of Pglycoprotein in dogs and cats. Vet Clin North Am Small Anim Pract. 2012;42(2):313-33.
[29] Conen S, Theunissen EL, Vermeeren A, van Ruitenbeek P, Stiers P, Mehta MA, et al. The role of P-glycoprotein in CNS antihistamine effects. Psychopharmacology (Berl). 2013. [Epub ahead of print]