Metoclopramide clinical studies

Clinical studies in cancer patients have also shown ondansetron to be a highly effective antiemetic drug and to be significantly more effective than metoclopramide [44-46]. As expected, there are no reports of extrapyrami-dal side-effects in patients receiving ondansetron. 

The number of clinical studies with A -THC is large and the field has recently been reviewed [ 146, 148] hence, only a few typical reports are mentioned here. In a 1980 study [157], 46 patients (9-70 years old) in a double-blind, crossover study were administered either A -THC (10 mg/m2 orally, three times daily) or prochlorperazine (10 mg, orally, three times daily). A -THC was more active than prochlorperazine, regardless of the emetogenicity of the chemotherapeutic agent, and young patients were more likely to have complete response than older patients. In a 1982 study [158], 27 adults in a double-blind study with A -THC (10 mg/m2, orally five times daily) and metoclopramide (2 mg/kg, i.v. five times daily) were compared. Metoclopramide was more potent than THC both as regards number and volume of emetic episodes. 

Most of the antiemetic clinical trials in the last decade have involved metoclopramide (1) either as a single agent or in combination with other drugs. Similarly, most of the chemical modification studies have been designed to optimize antiemetic and/or gastroprokinetic properties of metoclopramide and to eliminate undesirable CNS side-effects which are the consequence of its dopamine D2 receptor blockade [1-3]. 

In general, ketones, alcohols and ethers of formula (3) showed comparable protection against cisplatin-induced emesis in the dog and ferret with that of metoclopramide. Erythro (cis) alcohols (3c, 3g, 3i) were found to be more potent than the corresponding threo-(trans) isomers (3d, 3h, 3j). Optical isomer (.R) (3e) was found to be somewhat more potent than its (S )-enantiomer (3f) as an antagonist of cisplatin-induced emesis in the ferret. In the dog, both isomers showed similar activity. A number of heterocyclic analogues were also studied but with the exception of (3k), all were inferior in potency as antiemetic agents compared with other compounds (3) shown in Table 7.1. Lead compound, BMY 25801, batanopride, (3a) is presently under clinical investigation. 

Information seems to be limited to the reports cited. The most likely explanation for the discord between the cimetidine/suxamethonium results is that in the one study reporting increased suxamethonium effects some of the patients were also given metoclopramide, which can inhibit plasma cholinesterase and prolong the effects of suxamethonium (see also Neuromuscular blockers + Metoclopramide , p.l27). In four other studies, cimetidine and other H2-receptor antagonists did not alter suxamethonium effects. Therefore, it seems unlikely that an interaction exists. There is some evidence that cimetidine may slightly prolong the effects of vecuronium, but ranitidine appears not to interact. Atracurium and rocuro-nium appear not to be affected. Overall these possible interactions seem to be of little clinical significance. 

The clinical importance of the reduction in ketoprofen levels is unknown, but the authors of the study recommend that ketoprofen (and possibly other NSAIDs that are poorly soluble) should be t en 1 to 2 hours before metoclopramide. Conversely, for aspirin, tolfenamic acid, and other NSAIDs, metoclopramide can be used to increase the rate of absorption, and therefore possibly speed up the onset of analgesic effect in conditions such as migraine. 

A study in 8 healthy subjects found that a single 600-microgram dose of intravenous atropine reduced the rate of absorption of a single 400-mg oral dose of mexiletine, but the mexiletine AUC remained unaffected. Intravenous metoclopramide 10 mg hastened the absorption of mexiletine but similarly did not affect the AUC. Metoclopramide tended to reverse the effect of diamorphine on plasma mexiletine levels in one clinical trial (see also Mexiletine + Opioids , p.268). 

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. ... 

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