title: Pharmacokinetics, pharmacodynamics and toxicity of a combination of metoprolol succinate and telmisartan in Wistar albino rats: safety profiling.
abstract: Metoprolol succinate (MET), a cardioselective β blocker and telmisartan (TEL), an angiotensin receptor blocker were administered orally, both individually and in combination to Wistar albino rats for evaluation of their pharmacokinetics, pharmacodynamics and repeated dose oral toxicity (28 days). Pharmacokinetic study was performed by analyzing drug concentration in plasma by a developed and validated LC-MS/MS method following oral administration of MET and TEL at 2.5 mg/kg and 2.0 mg/kg dose, respectively, both individually and in combination. Antihypertensive activity of MET and TEL in above dose and manner was evaluated on artificially induced hypertension on laboratory animals. In repeated dose oral toxicity study, MET (60, 120 and 240 mg/kg/day) and/or TEL (12, 24 and 48 mg/kg/day) were administered to animals for 28 days followed by a recovery period of 14 days. Pharmacokinetic data revealed the probable absence of any pharmacokinetic interaction when co-administered. Improved blood pressure lowering effect was observed by combination therapy. Moreover, toxic effects obtained at high dose level of each treatment groups were transient and reversible and no evidence of additive toxic effects were observed due to concomitant administration. So, this combination can primarily be stated as safe which will be confirmed after clinical interaction studies in humans.
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
authors.forename: Utpal
authors.initials: U
authors.lastname: Nandi
authors.forename: Sanmoy
authors.initials: S
authors.lastname: Karmakar
authors.forename: Anjan Kumar
authors.initials: AK
authors.lastname: Das
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
authors.forename: Aswathi
authors.initials: A
authors.lastname: Padman
authors.forename: Nilendra
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Tapan Kumar
authors.initials: TK
authors.lastname: Pal
mesh_terms: D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D001565:Benzoates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry; D000077333:Telmisartan
chemical_list: D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D008790:Metoprolol; D000077333:Telmisartan