Investigating the Potential Effect of Commiphora myrrha on the Pharmacokinetics of Theophylline, a Narrow Therapeutic Index Drug

Abstract

Aim: The present study was conducted to investigate the effect of commonly used herb Commiphora myrrha on the pharmacokinetic profile of theophylline (narrow therapeutic index drug) in rabbits.

Methods: In the experimental groups, theophylline (16 mg/kg) was given orally to the rabbits. Where aqueous saline suspension of Commiphora myrrha (176 mg/kg, p.o.), was given to the rabbits and the blood samples were withdrawn at different time intervals (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h) from marginal ear vein after dosing and theophylline in plasma was analyzed by HPLC method.

Results: It was observed that there a significant differences in the C_max, AUC, AUMC, t_1/2, and MRT of theophylline when coadministered with Commiphora myrrha which indicate that the herb affect the metabolism and elimination when coadministered with theophylline.

Conclusion: Our results suggested that concurrent use of investigated herb alters the pharmacokinetics of theophylline. Confirmation of these results in human studies will warrant changes in theophylline dose or frequency when coadministered with herb under consideration.

Key words

bioavailability - cytochrome P4501A - disposition - herb-drug interaction

• References

• 1 Brink JA, Prior B, DaSilva EJ. Developing biotechnology around the world. Nat Biotechnol 1999; 17: 434-436
• 2 Azaizeh H, Saad B, Cooper E et al. Traditional Arabic and Islamic Medicine, a Re-emerging Health Aid. Evid Based Complement Alternat Med 2010; 7: 419-424
• 3 Hoareau L, DaSilva EJ. Medicinal plants: a re-emerging health aid. EJB Electronic journal of biotechnology 1999; 2: 56-70
• 4 Saad B, Azaizeh H, Said O. Tradition and perspectives of arab herbal medicine: a review. Evid Based Complement Alternat Med 2005; 2: 475-479
• 5 Omeish AF, Abbadi W, Ghanma IM et al. Hospital-based study on the use of herbal medicine in patients with coronary artery disease in Jordan. J Pak Med Assoc 2011; 61: 683-687
• 6 Tang J, Song X, Zhu M et al. Study on the pharmacokinetics drug-drug interaction potential of Glycyrrhiza uralensis, a traditional Chinese medicine, with lidocaine in rats. Phytother Res 2009; 23: 603-607
• 7 Shi S, Klotz U. Drug interactions with herbal medicines. Clin Pharmacokinet 2012; 51: 77-104
• 8 Tarirai C, Viljoen AM, Hamman JH. Herb-drug pharmacokinetic interactions reviewed. Expert Opin Drug Metab Toxicol 2010; 6: 1515-1538
• 9 Ohnishi A. A review of clinical use of theophylline in acute asthma: factors influencing kinetic disposition and drug interactions. Methods Find Exp Clin Pharmacol 2000; 22: 253-258
• 10 Page CP, Cotter T, Kilfeather S et al. Effect of chronic theophylline treatment on the methacholine dose-response curve in allergic asthmatic subjects. Eur Respir J 1998; 12: 24-29
• 11 Vergin H, Mahr G, Winterhalter B et al. Relative bioavailability and bioequivalence study of theophylline sustained release formulations. Arzneimittelforschung 2003; 53: 635-639
• 12 Sarkar MA, Hunt C, Guzelian PS et al. Characterization of human liver cytochromes P-450 involved in theophylline metabolism. Drug Metab Dispos 1992; 20: 31-37
• 13 Li XP, Zhang CL, Gao P et al. Effects of andrographolide on the pharmacokinetics of aminophylline and doxofylline in rats. Drug Res (Stuttg) 2013; 63: 258-262
• 14 Qiu F, Wang G, Zhao Y et al. Effect of danshen extract on pharmacokinetics of theophylline in healthy volunteers. Br J Clin Pharmacol 2008; 65: 270-274
• 15 Capasso R, Izzo AA, Pinto L et al. Phytotherapy and quality of herbal medicines. Fitoterapia 2000; 71 (Suppl. 01) S58-S65
• 16 Dolara P, Corte B, Ghelardini C et al. Local anaesthetic, antibacterial and antifungal properties of sesquiterpenes from myrrh. Planta Med 2000; 66: 356-358
• 17 Massoud A, El Sisi S, Salama O. Preliminary study of therapeutic efficacy of a new fasciolicidal drug derived from Commiphora molmol (myrrh). Am J Trop Med Hyg 2001; 65: 96-99
• 18 Al-Jenoobi FI, Ahad A, Mahrous GM et al. Effects of fenugreek, garden cress, and black seed on theophylline pharmacokinetics in beagle dogs. Pharmaceutical Biology 2014; DOI: 10.3109/13880209.2014.916312. (Article in press)
• 19 Ng TP, Wong ML, Hong CY et al. The use of complementary and alternative medicine by asthma patients. Qjm 2003; 96: 747-754
• 20 Fugh-Berman A. Herb-drug interactions. Lancet 2000; 355: 134-138
• 21 Landmark CJ, Patsalos PN. Interactions between antiepileptic drugs and herbal medicines. Bol Latinoam Caribe Plant Med 2008; 7: 108-118
• 22 Thabrew MI, Munasinghe TM, Chackrewarthi S et al. Possible interaction of herbal tea and carbamazepine. Drug Metabol Drug Interact 2003; 19: 177-187
• 23 Gu L, Gonzalez FJ, Kalow W et al. Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics 1992; 2: 73-77
• 24 Tang J, Sun J, Zhang Y et al. Herb-drug interactions: Effect of Ginkgo biloba extract on the pharmacokinetics of theophylline in rats. Food Chem Toxicol 2007; 45: 2441-2445
• 25 Brosen K. Drug interactions and the cytochrome P450 system. The role of cytochrome P450 1A2. Clin Pharmacokinet 1995; 29 (Suppl. 01) 20-25
• 26 Cupp MJ, Tracy TS. Cytochrome P450: new nomenclature and clinical implications. Am Fam Physician 1998; 57: 107-116
• 27 Smith TJ, Guo Z, Guengerich FP et al. Metabolism of 4-(methylnitro­samino)-1-(3-pyridyl)-1-butanone (NNK) by human cytochrome P4501A2 and its inhibition by phenethyl isothiocyanate. Carcinogenesis 1996; 17: 809-813
• 28 Bachmann K, Sanyal G, Potter J et al. In vivo evidence that theophylline is metabolized principally by CYP1A in rats. Pharmacology 1993; 47: 1-7
• 29 Faber MS, Jetter A, Fuhr U. Assessment of CYP1A2 activity in clinical practice: why, how, and when?. Basic Clin Pharmacol Toxicol 2005; 97: 125-134