High-dose drugs

Crison and Amidon [47,48] recently used the mass balance approach to study the variability in absorption due to intestinal transit time for water-insoluble drugs. As expected, for low dose drugs, such as digoxin, the variability in absorption sharply decreases with the increase of dissolution number via micronization. For high dose drugs, such as griseofulvin, little effect was observed when the dissolution number was increased by micronization. 

The problems of evaluating thyroid function during high dose drug exposure are well known for several... 

Cipolla, D. Boyd, B. Evans, R. Warren, S. Taylor, G. Farr, S.J. Bolus Administration of INS365 Studying the Feasibility of Delivering High Dose Drugs Using the AERx Pulmonary Delivery System. In Respiratory Drug Delivery VII Dalby, R.N., Byron, P.R., Farr, S.J., Peart, J., Eds. Interpharm Press, 2000 231-239. 

Hydrophilic matrix formulation of high-dose drugs (approximating 1.0g) is challenging because of the overall dosage weight limitations versus the quantity of the polymer required to achieve desired release profiles. It has been reported that very large tablets that are formulated to be swallowed whole (e.g. ER and delayed-release formulations) lead to poor patient compliance and therefore reduced market acceptability [50]. 

The linearity of the quantitation was tested for the practical application of a fast OPC approach with levels in the practical range from high therapeutic up to toxic plasma concentrations, typically comprising 0.1, 0.5, 2, 4 and 6 mg/L. Exceptions are the highly dosed drugs such as levetiracetam, lamotrigine, phenprocoumon or quetiapine (see Table 4.58). 

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