Intravenous and oral omeprazole: Why 40 mg is equivalent to 20 mg?
Omeprazol intravenoso y oral: ¿por qué 40 mg equivalen a 20 mg?
Key words: Therapeutic equivalency. Omeprazol. Sequential therapy.
Palabras clave: Equivalencia terapéutica. Omeprazol. Terapia secuencial.
Dear Editor,
It is a well-known fact the frequent use of intravenous daily doses of 40 mg omeprazole in adult patients in which the oral route is unsuitable and the usual exchange to an oral dose of 20 mg per day when the clinical situation improves. Although this recommendation is supported by a large number of sequential therapy programs, it appears necessary to review if this equivalence is correct or not (1-4). If the bioavailability of an intravenous drug is 100 %, then, in indications in which an oral dose of 20 mg would be enough for patients tolerating oral therapy -such as gastric ulcer prevention- why is it prescribed intravenous double doses of omeprazole?
]]> Although this reflection has been surely shared by many of us, we must admit that the riddle is still unsolved. The intravenous dose recommended by the manufacterer is 40 mg, so this is the dose that should be prescribed (5). However, in our opinion, there are some aspects that should be discussed.The first issue is related to both the omeprazole's pharmacokinetics and the time needed to achieve its maximum effect. In case of the oral formulation, the inhibitory effect of omeprazole on acid secretion increases with repeated once-daily dosing, reaching the maximum effect after 4-5 doses, whereas in the case of parenteral administration, 40 mg omeprazole produces on the first day of treatment a similar effect to that seen after repeated oral administration of 20 mg (5). Therefore, the equivalence between an intravenous dose of 40 mg and repeated oral doses of 20 mg seem clear. However, how is this equivalence maintained after successive intravenous doses of 40 mg? What effect would result from the administration of lower doses of intravenous omeprazole? In 1993, Cederberg et al. studied the effect of repeated once daily administration of 20 mg omeprazole orally and 10 mg and 40 mg intravenously (6). The result was an immediate and statistically significant reduction of intragastric acidity after the first intravenous dose of 40 mg, whereas the administration of successive doses of 40 mg only maintained the same reduction. Regarding the effect of intravenous doses of 10 mg and oral doses of 20 mg, the reduction obtained using both regimens was similar and increased with repeated administrations of the drug, that is, a single dose was not sufficient to inhibit an adequate number of H+/K+ ATPase pumps, while the effect obtained after the fifth dose was comparable to that obtained with the intravenous dose of 40 mg. Undoubtedly, it is curious to find out that long-term effects of daily administration of intravenous 40 mg and 10 mg omeprazole showed similar pharmacological effects; the two main differences observed between both doses are related to the onset of action (slower when using 10 mg) and plasma concentrations (greater when administering 40 mg but, as mentioned before, not related with a major clinical effect). Then, we can conclude that when a patient does not require an immediate maximum drug effect (which coincides with the majority of omeprazole indications (7) ), has a condition for which oral dosing with omeprazole 20 mg would be enough, and does not tolerate the oral route, a lower dose of intravenous omeprazole could become an alternative. In fact, the Intensive Care Unit of the Liverpool Health Service has already established the equivalence between an intravenous dose of 10 mg and an oral dose 20 mg of omeprazole (8).
The second aspect is related to indications for which the intravenous presentation has been specifically designed, that is, for those conditions in which there is clear evidence that higher doses of omeprazole are associated with greater clinical benefits and the oral route is commonly unsuitable, for example, gastrointestinal bleeding. So, how far have these indications influenced the prescription of intravenous doses of 40 mg to the rest of indications such as prophylaxis?
The question is open for debate.
Ana de Lorenzo-Pinto, Laura Delgado-Téllez-de-Cepeda,
María de los Ángeles Campos-Fernández-de-Sevilla and Carlos Martín-Español
Pharmacy Department. Hospital Universitario del Henares. Coslada, Madrid. Spain
References
]]>1. Implicaciones clínicas de la terapia secuencial. Complejo Hospitalario Universitario de Badajoz. Servicio de Farmacia (Internet). (citado 7 de abril de 2013). Disponible en: http://www.areasaludbadajoz.com/datos/farmacia/Sesi%C3%B3n_General_Farmacia_Hospitalaria_20112008_Terapia_Secuencial.pdf. [ Links ]
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]]>6. Cederberg C, Röhss K, Lundborg P, Olbe L. Effect of once daily intravenous and oral omeprazole on 24-hour intragastric acidity in healthy subjects. Scand J Gastroenterol 1993;28:179-84. [ Links ]
7. Barrera Linares E, Gómez Suárez E, Mataix Sanjuán A, Parramón Ponz M, Pascual Pérez JM, Revilla Pascual E, et al. Criterios de selección de Inhibidores de la Bomba de Protones. Servicio Madrileño de Salud (Internet). (citado 8 de abril de 2013). Disponible en: http://www.madrid.org/cs/Satellite?blobcol=urldata&blobheader=application%2Fpdf&blobheadername1=Content-Disposition&blobheadervalue1=filename%3DN3_01_2012.PDF&blobkey=id&blobtable=MungoB lobs&blobwhere=1310806965779&ssbinary=true. [ Links ]
8. Drug administration protocol. Omeprazole. Liverpool Health Service Intensive Care Unit. (Internet). (citado 7 de abril de 2013). Disponible en: http://intensivecare.hsnet.nsw.gov.au/five/doc/omeprazole_D_liverpool.pdf. [ Links ]
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