Gastro-oesophageal reflux disease (GORD) is a very common disorder of upper gastro-intestinal motility, differing widely in severity and prognosis. Medical therapy of GORD has involved antacids, alginates, prokinetic agents and antisecretory compounds, primarily H-2 receptor antagonists and proton pump inhibitors. Knowledge of the pharmacokinetics of these compounds is important, to optimise the therapeutic benefit in each patient. GORD patients are often elderly and pharmacokinetics are more variable in this group. Furthermore, they often suffer from other diseases needing medical therapy and may need a combination of drugs to heal reflux oesophagitis and relieve reflux symptoms. The ideal therapy for GORD will have linear pharmacokinetics, a relatively long plasma half-life (t 1/2), a duration of action allowing once daily administration, and a stable effect independent of interactions with food, antacids and other drugs. Over-the-counter antacids and alginates are widely used, but may affect absorption of H-2 receptor antagonists like cimetidine and ranitidine. Aluminium-containing antacids may, over time, cause toxicity in patients with renal insufficiency. In the treatment of CORD, cisapride presents important advantages over earlier prokinetic compounds, with a longer plasma t 1/2, low penetration of the blood-brain barrier and fewer adverse effects. The group of H-2 receptor antagonists is still the most frequently used therapy for GORD. Linear pharmacokinetics make dose adjustments easy and safe. In individual patients, suppression of gastric secretion is related to the area under the plasma concentration-time curve (AUC), but there is wide interindividual variation in the effect of the same oral dose. Only with frequent administration and high doses will acid suppression approximate that of proton pump inhibitors. Tolerance, with loss of effect over time, however, is most pronounced in this situation. H-2 receptor antagonists seem well suited for on-demand treatment of reflux symptoms, due to the rapid onset of effect and a decreased likelihood of the development of tolerance. Effervescent formulations provide more rapid absorption and almost immediate clinical effect. Cimetidine, however, causes interference with the metabolism of several other drugs in common use. In elderly patients elimination is delayed and in patients with renal insufficiency, dose reductions of all H-2 receptor antagonists are recommended. The most effective medical therapy for any severity of CORD, particularly in severe oesophagitis, are the proton pump inhibitors. The substituted benzimidazoles (omeprazole, lansoprazole and pantoprazole), an prodrugs which once trapped and activated in the acid milieu of the gastric glands potently suppress gastric secretion of acid and pepsin. Their long duration of action, more related to the slow turnover of parietal cell H+-K+ ATPase molecules, allows once daily administration in most patients. interindividual variation in bioavailability sometimes calls for higher doses or twice daily administration. Acid suppression is closely related to the AUC. Omeprazole is prone to interaction with the metabolism of other drugs, some of which may be clinically important. Lansoprazole seems to have an earlier onset of action than omeprazole, ascribed to higher bioavailability during the first days of treatment. Proton pump inhibitors have a slow onset of action, which makes them unsuited for on-demand therapy. Clinical practice in CORD calls for the use of not one but several substances, according to the severity and symptom pattern of the patient. Pharmacokinetic optimisation in the treatment of GORD is a question of selecting the most suitable substances and administration schemes within each group. Cisapride is superior to other prokinetics in ten-ns of longer plasma t 1/2 and less toxicity. Amongst H-2 receptor antagonists, the more long-acting compounds, ranitidine and famotidine, will improve acidity control throughout 24 hours and also cause less metabolic interaction with other drugs than cimetidine. Lansoprazole has a higher bioavailability than omeprazole from the first day of therapy, resulting in the more rapid relief of symptoms. Pantoprazole may cause fewer drug interactions than other proton pump inhibitors.
