Verapamil gastrointestinal effects

The effect of food on gastrointestinal transit and drug absorption of a multiparticular sustained release verapamil... 

The amount of verapamil presented to the liver, and its effective concentration in the region of the hepatic er zymes soon after oral dosing, are related to the rate at which verapamO is absorbed from the gastrointestinal tract into the portal vein and to the flow rate of blood in the portal vein to the liver. For instance, by hypothesizing a Michaelis-Menten metabolic process, when the absorption rate is slow and concentrations in the portal vein and liver are low, the hepatic metabolism of both enantiomers will be approximately first-order. Under these conditions, the K S ratio of the umnetabolized enantiomers leaving the liver will be closely related to the ratio of the Michaelis-Menten saturation constants (K ) for the enantiomers. The observed more rapid metabolism of S-verapamil than R-verapamil (i.e., S-verapamil has the lower systemic concentrations) is consistent with the lower reported for S-verapamil (16). 

Because of effects on smooth muscle, the calcium channel blockers (particularly verapamil (96) but also diltiazem) can cause constipation. This may be due to colonic motor activity inhibition (97). Gastroesophageal reflux can also occur, and the calcium channel blockers should be avoided in patients with symptoms suggestive of reflux esophagitis (98). Calcium channel blockers (verapamil, diltiazem, and nifedipine) can also be associated with an increased incidence of gastrointestinal bleeding, as reported in a prospective cohort study in 1636 older hypertensives, with a relative risk of 1.86 (95% Cl = 1.22, 2.82) compared with beta-blockers (7). However, this finding was not confirmed in other retrospective studies (13,99,100). 

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