METHODS: Hospitalised adult patients on EID gentamicin were selected. We considered a DFP of between 2 and 8 h as appropriate. Data from two blood samples (2 and 6 h postdose) from each patient were used to estimate the duration of DFP (i.e. DFP method 1). DFP was also calculated for the same patient using an empirically estimated elimination rate constant (Ke ) and the same 6 h postdose concentration value (DFP method 2). Correlation between the two methods was made. An alternative graphical method to estimate DFP was attempted.
KEY FINDINGS: Correlation between Ke and age was favourable (r = -0.453; P = 0.001). Ke derived from this empirical relationship was used to estimate DFP method 2. DFP method 1 correlated well with DFP method 2 (r = 0.742; P
METHODS: Hydrophilic pectin-sulphanilamide films, with or without oleic acid (OA), were subjected to drug release and skin permeation studies. The skins were untreated or microwave-treated, and characterized by infrared spectroscopy, Raman spectroscopy, thermal, electron microscopy and histology techniques.
RESULTS: Skin treatment by microwave at 2450 MHz for 5 min promoted drug permeation from OA-free film without incurring skin damage. Skin treatment by microwave followed by film loaded with drug and OA resulted in permeation of all drug molecules that were released from film. Microwave exerted spacing of lipid architecture of stratum corneum into structureless domains which was unattainable by OA. It allowed OA to permeate stratum corneum and accumulate in dermis at a greater ease, and synergistically inducing lipid/keratin fluidization at hydrophobic C-H and hydrophilic O-H, N-H, C-O, C=O, C-N regimes of skin, and promoting drug permeation.
CONCLUSION: The microwave technology is evidently feasible for use in promotion of drug permeation across the skin barrier. It represents a new approach in transdermal drug delivery.
MATERIALS AND METHODS: Five Malay patients receiving warfarin maintenance therapy were investigated for their CYP2C9*2, CYP2C9*3, and VKORC1-1639G>A genotypes and their vitamin K-dependent (VKD) clotting factor activities. The records of their daily warfarin doses and international normalized ratio (INR) 2 years prior to and after the measurement of VKD clotting factors activities were acquired. The mean warfarin doses were compared with predicted warfarin doses calculated from a genotypic-based dosing model developed for Asians.
RESULTS: A patient with the VKORC1-1639 GA genotype, who was supposed to have higher dose requirements, had a lower mean warfarin dose similar to those having the VKORC1-1639 AA genotype. This discrepancy may be due to the coadministration of celecoxib, which has the potential to decrease warfarins metabolism. Not all patients' predicted mean warfarin doses based on a previously developed dosing algorithm for Asians were similar to the actual mean warfarin dose, with the worst predicted dose being 54.34% higher than the required warfarin dose.
CONCLUSION: Multiple clinical factors can significantly change the actual required dose from the predicted dose from time to time. The additions of other dynamic variables, especially INR, VKD clotting factors, and concomitant drug use, into the dosing model are important in order to improve its accuracy.