Metoclopramide pharmacokinetics

Most pharmacokinetic interactions in transplantation occur due to interactions with the CYP enzyme system however, several interactions have been shown to occur via alternative mechanisms. One of the most notable is that seen between tacrolimus and some of the prokinetic agents. Cisapride and metoclopramide have been shown to increase the absorption of tacrolimus by enhancing gastric emptying.41... 

Pharmacology Metoclopramide stimulates motility of the upper Gl tract without stimulating gastric, biliary, or pancreatic secretions. Its mode of action is unclear. Pharmacokinetics ... 

Shukla UA, Pittman KA, Barbhaiya RH. Pharmacokinetic interactions of cefprozil with food, propantheline, metoclopramide, and probenecid in healthy volunteers. J Clin Pharmacol 1992 32 725-731. 

Bernardi M, Tame MR, Albani F, et al. (1991) Pharmacokinetics of metoclopramide after single oral dose administration in cirrhosis. Eur J Gastroenterol Hepatol 3 519-522. 

Feurle GE (1990) Arteriovenous shunting and cholestasis in hepatic hemangiomatosis associated with metoclopramide. Gastroenterology 99 258-262. Magueur E, Horgege H, Attali P, et al. (1991) Pharmacokinetics of metoclopramide in patients with liver cirrhosis. Br J Clin Pharmacol 31 185-187. Albani F, Tame MR, De Palma R, et al. (1991) Kinetics of intravenous metoclopramide in patients with hepatic cirrhosis. Eur ] Clin Pharmacol 40 423-425. 

Kirch W, Janisch HD, Santos SR, Duhrsen U, Dylewicz P, Ohnhaus EE. Effect of cisapride and metoclopramide on digoxin bioavailability. Eur J Drug Metab Pharmacokinet 1986 ll(4) 249-50. 

Although metoclopramide has lost some ground to newer congeners, it has been the most widely used of the neuroleptic-type antiemetic drugs and is therefore the one for which the clearest picture of adverse effect, typically neuroleptic and endocrine effects, has emerged. Reactions are generally short-lived provided treatment is withdrawn the duration of reactions does not always seem to be explained by simple pharmacokinetic considerations. 

Magueur E, Hagege H, Attali P, Singlas E, Etienne JP, Taburet AM. Pharmacokinetics of metoclopramide in patients with liver cirrhosis. Br J Clin Pharmacol 1991 31(2) 185-7. 

Bateman DN, Kahn C, Mashiter K, Davies DS. Pharmacokinetic and concentration-effect studies with intravenous metoclopramide. Br J Clin Pharmacol 1978 6(5) 401-7. 

Pharmacokinetics All oral PPIs are rapidly absorbed and undergo hepatic metabolism. The bioavailability of the oral PPIs ranges from 30% to 85%. All of the PPIs have a short elimination PA (< 2 hr), but this has minimal effect on the duration of antisecretory action due to irreversible binding to the proton pump. Both cisapride and metoclopramide have a rapid onset of action, < 1 hr. Both agents have a similar oral bioavailability 50%-80% and are extensively metabolized by the liver to inactive metabolites. 

Ross-Lee LM, Eadie MJ, Heazlewood V, Bodmer F, Tyrer JH. A irin pharmacokinetics in migraine the effect of metoclopramide. EurJCtin Pharmacol (19S3 ) 24,777-85. 

Etman MA, Ismail FA, Nada AH. Effect of metoclopramide on ketoprofen pharmacokinetics in man. IntJPharmaceutics ( 992) 88,433-5. 

Vachharajani NN, Sh3ni WC, Barbhaiya RH. Pharmacokinetic interaction between butorphanol nasal spray and oral metoclopramide in healdiy women. J Clin Pharmacol (1997) 37,979-85. 

Na Bangchang K, Karbwang J, Bunnag D, Harinasuta T, Back DJ, The effect of metoclopramide on mefloquine pharmacokinetics. BrJ Clin Pharmacol (1991) 32, 640-1,... 

The pharmacokinetics of cefprozil are minimally affected by propantheline and metoclopramide, and an interaction of clinical importance is unlikely. ... 

Bergan T, Mastropaolo G, Di Mario F, Naccarato R Pharmacokinetics of fosfomycin and influence of cimetidine and metoclopramide on tiie bioavailability of fosfomycin trometamol. New Trends in Urinary Tract Infections (eds Neu and Williams) Int Symp Rome 1987, pp 157-66. Published in 1988. 

In a randomised, crossover study, 15 healthy subjects were given single 10-mg doses of zolmitriptan alone or with metoclopramide 10 mg. Metoclopramide had no effect on the pharmacokinetics of zolmitriptan, so there would appear to be no reason for avoiding concurrent use of these two drugs. ... 

Kopitar Z, Vrhovac B, Povsic L, Plavsic F, Francetic I, Urbancic J. The effect of food and metoclopramide on the pharmacokinetics and side effects of bromocriptine. EurJDrugMetab Phamacokinet ( 99 ) 16, 177-81. 

Loperamide and metoclopramide do not appear to aiter didanosine pharmacokinetics. 

In 6 men and 6 women who were HIV-positive, the pharmacokinetics of oral buffered didanosine 300 mg were not altered to a clinically relevant extent by 4 mg of loperamide, given 19,13,7 and 1 hour before the didanosine. The rate of didanosine absorption was slightly decreased but the extent of absorption was unchanged. Similarly, the pharmacokinetics of oral buffered didanosine 300 mg were found to be unaffected by 10 mg of intravenous metoclopramide. It appears that neither delaying nor accelerating gastrointestinal transit time appreciably alters the pharmacokinetics of didanosine, which is acid labile. On the basis of this study the authors conclude that neither the dose nor the frequency of didanosine administration need be altered if either loperamide or metoclopramide is given concurrently. ... 

Knupp CA, Milbrath RL, Barbhaiya RH. Effect of metoclopramide and loperamide on the pharmacokinetics of didanosine in HIV seropositive asymptomatic male and female patients. Eur J Clin Pharmacol (1993) 45, 409-13. 

Oral metoclopramide syrup 20 mg, given 30 minutes before sustained-re-lease propranolol 160 mg, had no effect on the pharmacokinetics of propranolol in 12 healthy subjects. In contrast, an earlier brief report found that the rate of absorption of a conventional formulation of propranolol 80 mg was increased by intravenous metoclopramide 10 mg in 4 healthy subjects. In the first 2 hours after dosing, propranolol levels were increased by 1.3 to 2.5-fold. However, these changes are unlikely to be clinically relevant. 

Metoclopramide 10 mg four times daily did not alter the pharmacokinetics of a single 750-microgram intravenous dose of palonosetron in healthy subjects. ... 

H. Lamparczyk, A. Chmielewska, L. Konieczna, A. Plenis and P.K. Zarzycki, RP-HPLC method with electrochemical detection for the determination of metoclopramide in serum and its use in pharmacokinetic studies, Biomed. Chromatogr., 2001, 15, 513-517. 

H.S. Mahajan and S. Gattani, In situ gels of metoclopramide hydrochloride for intranasal delivery In vitro evaluation and in vivo pharmacokinetic study in rabbits. Drug Deliv., 17 19-27, 2010. 

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