Pharmacokinetic parameters for liver and kidney were estimated using the tissue concentration–time profiles for each route of administration. Pharmacokinetic parameters were determined from the blood concentration–time profiles for each route of administration and each soluble receptor preparation ( Gustavson et al., 1989). Lynch, in International Review of Experimental Pathology, 1993 B Pharmacokinetic Data Analysis 82 Other calcium channel blockers do not usually cause clinically significant changes in concomitant drug concentrations, and dose modification is usually not required.Ĭindy A. This interaction has been exploited so that the calcium channel blocker is used as an immunosuppressant-sparing agent. Verapamil and diltiazem are moderately potent inhibitors, and dose modification and monitoring of the concomitant drug are required. To varying extents, calcium channel blockers inhibit CYP3A4 and P-glycoprotein, causing increased absorption and reduced elimination of various substrate drugs, including cyclosporine, tacrolimus, sirolimus, and everolimus. Dihydropyridine calcium channel blockers can cause significant edema, which can aggravate the edema of renal impairment. They are generally well tolerated and used in normal doses according to response. Pharmacokinetic parameters of calcium channel blockers are essentially unaltered in renal impairment. Russ, in Comprehensive Clinical Nephrology (Fourth Edition), 2010 Calcium Channel Blockers mAbs, therapeutic proteins, and peptides, in general, have moderate to high bioavailability (∼30–100%). Bioavailability following SC or IM administration is highly variable with biopharmaceuticals. Clearance is more rapid and half-lives are shorter (minutes to hours) and more variable for therapeutic proteins and peptides. Parameters for antibody fragments overlap the range of values for therapeutic proteins and peptides, reflecting similar molecule size and clearance pathways. Unmodified mAbs typically have slow clearance and long terminal half-lives (days to weeks) ( Table 4.2). Selected representative PK parameters and example serum concentration profiles for mAbs, therapeutic proteins, peptides, and modified molecules are provided in Table 4.2 and Figures 4.2, 4.5, and 4.6. Limited reviews are available for therapeutic proteins and peptides and data are available for individual molecules or molecule types. PK parameters for mAbs have been summarized in a number of recent reviews.
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