The bioavailability of bromazepam, omeprazole and paracetamol given by nasogastric feeding tube.
OBJECTIVE
To characterize and compare the pharmacokinetic profiles of bromazepam, omeprazole and paracetamol when administered by the oral and nasogastric routes to the same healthy cohort of volunteers.


METHODS
In a prospective, monocentric, randomized crossover study, eight healthy volunteers received the three drugs by the oral (OR) and nasogastric routes (NT). Sequential plasma samples were analyzed by high-performance liquid chromatography-UV, pharmacokinetic parameters (Cmax, AUC(0-infinity), t(1/2), k(e), tmax) were compared statistically, and Cmax, AUC(0-infinity) and t(max) were analyzed for bioequivalence.


RESULTS
A statistically significant difference was seen in the AUC(0-infinity) of bromazepam, with nasogastric administration decreasing availability by about 25%: AUC(OR) = 2501 ng mL(-1) h; AUC(NT) = 1855 ng mL(-1) h (p < 0.05); ratio (geometric mean) = 0.74 [90% confidence interval (CI) 0.64-0.87]. However, this does not appear to be clinically relevant given the usual dosage range and the drug's half-life (approx. 30 h). A large interindividual variability in omeprazole parameters prevented any statistical conclusion from being drawn in terms of both modes of administration despite their similar average profile: AUC(OR) = 579 ng mL(-1) h; AUC(NT) = 587 ng mL(-1) h (p > 0.05); ratio (geometric mean) = 1.01 (90% CI 0.64-1.61). An extended study with a larger number of subjects may possibly provide clearer answers. The narrow 90% confidence limits of paracetamol indicate bioequivalence: AUC(OR) = 37 microg mL(-1) h; AUC(NT) = 41 microg mL(-1) h(p > 0.05); ratio (geometric mean) = 1.12 (90% CI 0.98-1.28).


CONCLUSIONS
The results of this study show that the nasogastric route of administration does not appear to cause marked, clinically unsuitable alterations in the bioavailability of the tested drugs.
Podilsky
Gregory
G
Department of Pharmacy, University Hospital Centre, Rue du Bugnon 46, Lausanne 1011, Switzerland.
Berger-Gryllaki
Markoulina
M
Testa
Bernard
B
Buclin
Thierry
T
Roulet
Michel
M
Pannatier
Andre
A
D000082:Acetaminophen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001960:Bromazepam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015331:Cohort Studies; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D007441:Intubation, Gastrointestinal; D008297:Male; D008657:Metabolic Clearance Rate; D009853:Omeprazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011446:Prospective Studies; D015203:Reproducibility of Results; D013810:Therapeutic Equivalency
D018712:Analgesics, Non-Narcotic; D014151:Anti-Anxiety Agents; D000897:Anti-Ulcer Agents; D000082:Acetaminophen; D009853:Omeprazole; D001960:Bromazepam