gms | German Medical Science

Objective: Patients with high grade subarachnoid hemorrhage (SAH) are considered critically ill. Complications in various organ systems often occur here, in particular dysfunction of the gastrointestinal tract can lead to an insufficient absorption of enterally administered drugs such as nimodipine. The aim of this study was to determine whether and to what extent dysfunction of the gastrointestinal tract influences the absorption of enterally administered drugs in patients with high grade SAH.

Methods: We prospectively enrolled 12 patients with high grade SAH (H&H Grade III to IV) in the study. The control group consisted of 13 otherwise healthy patients, who electively underwent a cranial surgical intervention on day 2 after admission. Patients in both groups received esomeprazole either orally or through a gastric tube during hospital stay except for day 4 after admission, on which the drug was administered intravenously allowing us to estimate oral bioavailability. Esomeprazole serum concentrations were measured on days 1, 3, 4 in both groups and additionally on day 7 after admission in the study group. Pharmacokinetics of esompeprazole were compared between the SAH and control groups with area under the curve (AUC), Cmax and bioavailability as parameters of primary interest.

Results: Mean age of the study and control groups was 59±10 years and 58±12 years respectively. In the study group on days 1, 3 and 7, AUC values were 51±74, 113±99 and 39±35 mg*min/L, respectively; Cmax values were 172±201, 462 ±453 and 224 ±182 µg/L, respectively and bioavailability values were 20±26, 41±30 and 22±15% respectively. In the control group on day 1 and 3, AUC values were 206±99 and 146±81 mg*min/L, respectively; Cmax values were 1013±474 and 735±443 µg/L, respectively and bioavailability was 66±33 and 53±31 respectively. AUC, Cmax, and bioavailability of esompeprazole in the study group on days 1 and 7 were significantly lower than those in the control group, p<0,001.

Conclusion: Patients in with high grade SAB had severely restricted drug absorption. In the majority of SAH patients, no improvement in the resorption capacity was found even one week after onset of hemorrhage. Consecutively, clearly inadequate effects of enterally administered medication must be expected in this group of patients.