The bioavailability of nasogastric versus tablet-form oral trovafloxacin in healthy subjects

BACKGROUND: Patients in the hospital, as well as those in home care setting s, 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 alternat ive to oral antibiotic administration. However, delivery of crushed oral fo rmulations of drugs via nasogastric tubes is often carried out without adeq uate 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-o ver study, 24 healthy volunteers were given one dose of leach of the follow ing treatments, with a 7-day washout between dosing periods: Treatment A: t wo 100-mg trovafloxacin tablets given orally with 240 mL water; Treatment B : two crushed 100-mg trovafloxacin tablets suspended in water and administe red through a nasogastric tube into the stomach; Treatment C: two crushed 1 00-mg trovafloxacin tablets suspended in water and administered through a n asogastric tube into the duodenum; or Treatment D: two crushed 100-mg trova floxacin tablets suspended in water and given through a nasogastric tube in to the stomach concomitantly with an enteral feeding solution (240 mt full- strength Osmolite). RESULTS: Pharmacokinetic analyses showed that the bioavailability of trovaf loxacin after administration of crushed tablets into the stomach with or wi thout 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%. Res ults of analysis of variance (ANOVA) indicated no significant sequence, per iod, or treatment-by-period interaction effects. Administration of trovaflo xacin into the duodenum (Treatment C) resulted in reduced systemic exposure to trovafloxacin, with a 31% decrease in AUC(0-infinity) and a 30% decreas e in peak serum concentration (C-max) compared to oral administration. Time to peak serum concentration (T-max) was 1.7 hours after oral administratio n of trovafloxacin and 1.1 hours after administration directly into the sto mach or duodenum through a nasogastric tube in the absence of concomitant e nteral feeding. All four treatments were well tolerated; no participant dis continued the study due to adverse events and no serious adverse events wer e reported. CONCLUSIONS: These results showed that administration of crushed trovafloxa cin tablets through a nasogastric tube into the stomach, with or without co ncomitant enteral feeding, achieves absorption and tolerability comparable to those of orally administered trovafloxacin tablets. (C) 1998 by Excerpta Medica, Inc.