Aims: This review describes clinical results of gastrointestinal intubation studies of eight controlled release (CR) candidates under development during the 1990s and offers suggestions for determining why, when and how to conduct human intubation studies.
Methods: Experience with the administration of the following eight compounds to various regions of the gastrointestinal tract is described: CJ-13,610, CP-195,543, CP-331,684, CP-409,092, CP-424,391, azithromycin, sertraline, and trovafloxacin. Also included are human pharmacokinetic studies with prototype CR dosage forms for CJ-13,610 and CP-424,391.
Results: Intubation studies, while appearing invasive, are safe and not unpleasant procedures that have been found to be valuable in the development of CR formulations.
Conclusions: The following recommendations are made regarding intubation studies: (i) no intubation study is recommended for compounds with high permeability, since these compounds are likely to be well absorbed from the colon; (ii) compounds with moderate permeability may require an intubation study if the dog colon and in silico models predict a marginally acceptable CR concentration-time profile; (iii) use a dose that approximates 1 h of the intended CR delivery rate; (iv) use the smallest volume possible; (v) define and record tubing placement; (vi) use a thermodynamically stable solution or/and suspension.