BACKGROUND:Patients in the hospital, as well as those in home care settings, often require nutritional supplementation with enteral feeding solutions. In addition, patients with serious infections who are clinically unstable often cannot maintain adequate intake by mouth and may require an alternative to oral antibiotic administration. However, delivery of crushed oral formulations of drugs via nasogastric tubes is often carried out without adequate bioavailability data, and this method of administration may not always be equivalent to oral drug delivery. METHODS: In an open-label, randomized, four-period, four-treatment, cross-over study, 24 healthy volunteers were given one dose of each of the following treatments, with a 7-day wash-out between dosing periods: Treatment A: two 100-mg trovafloxacin tablets given orally with 240 mL water; Treatment B: two crushed 100-mg trovafloxacin tablets suspended in water and administered through a nasogastric tube into the stomach; Treatment C: two crushed 100-mg trovafloxacin tablets suspended in water and administered through a nasogastric tube into the duodenum; or Treatment D: two crushed 100-mg trovafloxacin tablets suspended in water and given through a nasogastric tube into the stomach concomitantly with an enteral feeding solution (240 mL full-strength Osmolite). RESULTS: Pharmacokinetic analyses showed that the bioavailability of trovafloxacin after administration of crushed tablets into the stomach with or without concomitant enteral feeding was not significantly different from that of the orally administered whole tablets: the 90% confidence limits of the area under the concentration-time curve (AUC(0-infinity)) for Treatment B versus Treatment A (91.3%, 109.5%) and Treatment D versus Treatment A (91.6%, 109.9%) were well within the bioequivalence criteria of 80% to 125%. Results of analysis of variance (ANOVA) indicated no significant sequence, period, or treatment-by-period interaction effects. Administration of trovafloxacin into the duodenum (Treatment C) resulted in reduced systemic exposure to trovafloxacin, with a 31% decrease in AUC(0-infinity) and a 30% decrease in peak serum concentration (Cmax) compared to oral administration. Time to peak serum concentration (Tmax) was 1.7 hours after oral administration of trovafloxacin and 1.1 hours after administration directly into the stomach or duodenum through a nasogastric tube in the absence of concomitant enteral feeding. All four treatments were well tolerated; no participant discontinued the study due to adverse events and no serious adverse events were reported. CONCLUSIONS: These results showed that administration of crushed trovafloxacin tablets through a nasogastric tube into the stomach, with or without concomitant enteral feeding, achieves absorption and tolerability comparable to those of orally administered trovafloxacin tablets.
RCT Entities:
BACKGROUND:Patients in the hospital, as well as those in home care settings, often require nutritional supplementation with enteral feeding solutions. In addition, patients with serious infections who are clinically unstable often cannot maintain adequate intake by mouth and may require an alternative to oral antibiotic administration. However, delivery of crushed oral formulations of drugs via nasogastric tubes is often carried out without adequate bioavailability data, and this method of administration may not always be equivalent to oral drug delivery. METHODS: In an open-label, randomized, four-period, four-treatment, cross-over study, 24 healthy volunteers were given one dose of each of the following treatments, with a 7-day wash-out between dosing periods: Treatment A: two 100-mg trovafloxacin tablets given orally with 240 mL water; Treatment B: two crushed 100-mg trovafloxacin tablets suspended in water and administered through a nasogastric tube into the stomach; Treatment C: two crushed 100-mg trovafloxacin tablets suspended in water and administered through a nasogastric tube into the duodenum; or Treatment D: two crushed 100-mg trovafloxacin tablets suspended in water and given through a nasogastric tube into the stomach concomitantly with an enteral feeding solution (240 mL full-strength Osmolite). RESULTS: Pharmacokinetic analyses showed that the bioavailability of trovafloxacin after administration of crushed tablets into the stomach with or without concomitant enteral feeding was not significantly different from that of the orally administered whole tablets: the 90% confidence limits of the area under the concentration-time curve (AUC(0-infinity)) for Treatment B versus Treatment A (91.3%, 109.5%) and Treatment D versus Treatment A (91.6%, 109.9%) were well within the bioequivalence criteria of 80% to 125%. Results of analysis of variance (ANOVA) indicated no significant sequence, period, or treatment-by-period interaction effects. Administration of trovafloxacin into the duodenum (Treatment C) resulted in reduced systemic exposure to trovafloxacin, with a 31% decrease in AUC(0-infinity) and a 30% decrease in peak serum concentration (Cmax) compared to oral administration. Time to peak serum concentration (Tmax) was 1.7 hours after oral administration of trovafloxacin and 1.1 hours after administration directly into the stomach or duodenum through a nasogastric tube in the absence of concomitant enteral feeding. All four treatments were well tolerated; no participant discontinued the study due to adverse events and no serious adverse events were reported. CONCLUSIONS: These results showed that administration of crushed trovafloxacin tablets through a nasogastric tube into the stomach, with or without concomitant enteral feeding, achieves absorption and tolerability comparable to those of orally administered trovafloxacin tablets.