Shortcomings of the first-generation proton pump inhibitors

Proton pump inhibitors (PPIs) are widely prescribed for the treatment of ga stro-oesophageal reflux disease (GORD) as well as gastric and duodenal ulce rs, and these agents are now considered the drugs of choice for managing su ch acid-related disorders, Despite their well-documented efficacy and safet y, first-generation PPIs (omeprazole, pantoprazole and lansoprazole) have n otable limitations. These drugs exhibit substantial interpatient variabilit y in pharmacokinetics and may have significant interactions with other drug s, The time of dosing and ingestion of meals may also influence the pharmac okinetics of these agents as well as their ability to suppress gastric acid secretion. First-generation PPIs also have a relatively slow onset of phar macological action and may require several doses to achieve maximum acid su ppression and symptom relief, possibly limiting their usefulness in on-dema nd GORD therapy. First-generation PPIs may also fail to provide 24-h suppre ssion of gastric acid, and noctural acid breakthrough can occur even with t wice-daily dosing. Both first- and second-generation PPIs may be associated with adverse events consequent to gastric acid suppression, but newer PPIs have the potential to overcome some critical pharmacokinetic, pharmacodyna mic, and clinical limitations of the first-generation drugs. Eur J Gastroen terol Hepatol 13 (suppl 1):S29-S33 (C) 2001 Lippincott Williams & Wilkins.