Plasma Double-peak Phenomenon Following Oral Administration

Abstract

Abstract: The plasma concentration-time curves of many drugs often show a double-peak or mutiple-peak phenomenon after oral administration. The non-uniformly rate of drug disintegrate and release from the dosage form and lipid solubility may be the common causes of this matter. Enterohepatic circulation and gastric pH were thought to be the two main factors for the double-peak phenomenon from Physiology Perspective. According to the lasted report,there were multiple mechanism of double-peak phenomenon and the greater part of them have been controversial, mainly include that gastricmotility, multiple gastrointestinal tract absorption site, uneven distribution of P-glycoprotein in gut and so on. The main purpose of the article is summarizing the research situation of the mechanism of this phenomenon to provide reference for clinical safe drug use.

Key words: double-peak phenomenon, enterohepatic circulation, P-glycoprotein, delayed gastric emptying, gastrointestinal motility

CLC Number:

R969.1

WANG Yan, YANG Guo-ping, GUO Cheng-xian, PEI Qi, ZHANG Ran-ran, HUANG Lu. Plasma Double-peak Phenomenon Following Oral Administration[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(3): 341-345.

References

[1] 居文正,张军,谈恒山,等.高效液相质谱联用法(HPLC-MS)测定灯盏乙素血药浓度及其临床药代动力学研究[J].中国临床药理学与治学,2005,10(3):298-301.
[2] Kimira Y, Tajima K, Ohta A, et al. Synergistic effect of isoflavone glycosides and fructooligosaccharides on postgastrectomy osteopenia in rats[J]. J Clin Biochem Nutr, 2012, 51(2):156-160.
[3] Qu J, Gao J, Sun J, et al. Pharmacokinetics of conjugated metabolites in rat plasma after oral administration of tectoridin[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2012,902(1): 61-69.
[4] Takamatsu N, Welage LS, Hayashi Y, et al. Variability in cimetidine absorption and plasma double peaks following oral administration in the fasted state in humans: correlation with antral gastric motility[J]. Eur J Pharm Biopharm, 2002, 53(1): 37-47.
[5] Wang Y, Roy A, Sun L, et al.A double-peak phenomenon in the pharmacokinetics of alprazolam after oral administration[J]. Drug Metab Dispos, 1999,27(8):855-859.
[6] Metsugi Y, Miyaji Y, Ogawara K, et al. Appearance of double peaks in plasma concentration-time profile after oral administration depends on gastric emptying profile and weight function[J]. Pharm Res, 2008,25(4): 886-895.
[7] Sanaka M, Yamamoto T, Tsutsumi H, et al. Wagner-Nelson method for analysing the atypical double-peaked [13CO2] excretion curve in the [13C] -octanoate gastric emptying breath test in humans[J]. Clin Exp Pharmacol Physiol, 2005, 32(7): 590-594.
[8] Nasiri-Toosi Z, Dashti-Khavidaki S, Nasiri-Toosi M, et al. Clinical pharmacokinetics of oral versus sublingual administration of tacrolimus in adult liver transplant recipients[J]. Exp Clin Transplant, 2012,10(6): 586-591.
[9] Lainesse C, Frank D, Meucci V, et al. Pharmacokinetics of clomipramine and desmethylclomipramine after single-dose intravenous and oral administrations in cats[J]. J Vet Pharmacol Ther, 2006,29(4): 271-278.
[10] Belle DJ, Callaghan JT, Gorski JC, et al. The effects of an oral contraceptive containing ethinyloestradiol and norgestrel on CYP3A activity[J]. Br J Clin Pharmacol, 2002, 53(1): 67-74.
[11] Godfrey KR, Arundel PA, Dong Z, et al. Modelling the Double Peak Phenomenon in pharmacokinetics[J]. Comput Methods Programs Biomed, 2011,104(2): 62-69.
[12] Schaiquevich P, Niselman A, Rubio M. Comparison of two compartmental models for describing ranitidine's plasmatic profiles[J]. Pharmacol Res, 2002, 45(5): 399-405.
[13] Xitian P, Hongying L, Kang W, et al. A novel remote controlled capsule for site-specific drug delivery in human GI tract[J]. Int J Pharm, 2009, 382(1/2): 160-164.
[14] Liu HY, Pi XT, Zheng XL, et al. Pharmacokinetics of aminophylline delivered to the small intestine and colon using remote controlled capsules[J]. Chin Med J (Engl), 2010,123(3): 320-325.
[15] Chauhan MS, Kumar A, Pathak K. Osmotically regulated floating asymmetric membrane capsule for controlled site-specific delivery of ranitidine hydrochloride: optimization by central composite design[J]. AAPS PharmSciTech, 2012,13(4): 1492-1501.
[16] Yalavarthi PR, Vulava J, Vadlamudi HC, et al. Modified Pulsincap of Ibuprofen - A Novel Approach for Chronotherapy[J]. Curr Drug Deliv, 2013,10(3): 299-307.
[17] Oo C, Snell P, Barrett J, et al. Pharmacokinetics and delivery of the anti-influenza prodrug oseltamivir to the small intestine and colon using site-specific delivery capsules[J]. Int J Pharm, 2003,257(1/2): 297-299.
[18] Stappaerts J, Annaert P, Augustijns P. Site dependent intestinal absorption of darunavir and its interaction with ketoconazole[J]. Eur J Pharm Sci, 2013, 49(1): 51-56.
[19] Wada S, Kano T, Mita S, et al. Role of inter-segmental differences in P-glycoprotein expression and activity along rat small intestine in causing double-peak phenomena of substrate plasma concentration[J]. Drug Metab Pharmacokinet, 2013, 28(2): 98-103.
[20] Li LY, Amidon GL, Kim JS, et al. Intestinal metabolism promotes regional differences in apical uptake of indinavir: coupled effect of P-glycoprotein and cytochrome P450 3A on indinavir membrane permeability in rat[J]. J Pharmacol Exp Ther, 2002, 301(2): 586-593.
[21] 冉启文. P-糖蛋白与药物的结合体在体内的转化过程探讨[J].中国现代应用药学, 2008,25(7): 618-622.
[22] Mouly S, Paine MF. P-glycoprotein increases from proximal to distal regions of human small intestine[J]. Pharm Res, 2003, 20(10): 1595-1599.
[23] Cusack SL, Reginald P, Hemsen L, et al. The pharmacokinetics and safety of an intraoperative bupivacaine-collagen implant (XaraColl((R)) for postoperative analgesia in women following total abdominal hysterectomy[J]. J Pain Res, 2013, 6: 151-159.
[24] Hu D, Onel E, Singla N, et al. Pharmacokinetic profile of liposome bupivacaine injection following a single administration at the surgical site[J]. Clin Drug Investig, 2013, 33(2): 109-115.
[25] Larsen AT, Ohlsson AG, Polentarutti B, et al. Oral bioavailability of cinnarizine in dogs: relation to SNEDDS droplet size, drug solubility and in vitro precipitation[J]. Eur J Pharm Sci, 2013, 48(1/2): 339-350.
[26] Ogasawara A, Kume T, Kazama E. Effect of oral ketoconazole on intestinal first-pass effect of midazolam and fexofenadine in cynomolgus monkeys[J]. Drug Metab Dispos, 2007, 35(3): 410-418.
[27] Uno T, Ohkubo T, Sugawara K, et al. Effects of grapefruit juice on the stereoselective disposition of nicardipine in humans: evidence for dominant presystemic elimination at the gut site[J]. Eur J Clin Pharmacol, 2000,56(9/10): 643-649.
[28] Jin M, Shimada T, Yokogawa K, et al. Site-dependent contributions of P-glycoprotein and CYP3A to cyclosporin A absorption, and effect of dexamethasone in small intestine of mice[J]. Biochem Pharmacol, 2006, 72(8): 1042-1050.
[29] Fang X, Liu X, Liu W, et al. Pharmacokinetics of enrofloxacin in allogynogenetic silver crucian carp, Carassius auratus gibelio[J]. J Vet Pharmacol Ther, 2012, 35(4): 397-401.
[30] Shaffer CL, Ryder TF, Venkatakrishnan K, et al. Biotransformation of an alpha4beta2 nicotinic acetylcholine receptor partial agonist in sprague-dawley rats and the dispositional characterization of its N-carbamoyl glucuronide metabolite[J]. Drug Metab Dispos, 2009,37(7): 1480-1489.
[31] Mirfazaelian A, Mahmoudian M. A simple pharmacokinetics subroutine for modeling double peak phenomenon[J]. Biopharm Drug Dispos, 2006, 27(3): 119-124.