XXXX : pharmacokinetics and detailed studies of plasma and erythrocyte binding during intravenous and oral administration.

@entity1 @entity205 @entity412 @entity165
On the basis that unbound concentration better correlates with response than total plasma or blood concentration, the inter- and intra-subject variability in the distribution of @entity205 within blood and to plasma components was studied in renal transplant @entity1 . Pharmacokinetic aspects were also studied. Blood samples were analysed from @entity1 who received the drug both by a 72-h i.v. infusion and orally (7 mg.kg-1 twice daily). Steady-state was reached within 18 h of starting the i.v. infusion; the plasma data were best fitted by a biexponential equation with half-times of 0.13-1.02 h and 4.3-13.9 h, associated with the two phases. The mean plasma clearance was 700 ml/min. Concentrations during the infusions measured by RIA and HPLC were comparable. Oral profiles showed rapid and extensive absorption. The peak plasma concentrations were 1460-1880 micrograms.l-1 and occurred 2-4 h after dosing, with bioavailability estimates of 41-113%. Concentrations measured by RIA were higher than by HPLC. Blood-to-plasma concentration ratio measurements of @entity205 at 37 degrees C decreased with increasing plasma concentration and increased with haematocrit. Fraction unbound, measured by ultra-centrifugation, was in the range 0.042-0.122 with an average of 0.068, and varied little in some @entity1 but showed systematic changes with time in others. @entity205 binding was found to be related not only to the @entity412 but, more particularly, to the @entity165 -related lipoproteins in plasma. Monitoring @entity165 may be helpful in identifying @entity1 with extremes in binding or with widely varying binding.
