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The effect of renal function on the pharmacokinetics of ranitidine (1994)

Dixon, J. S. ; Borg-Costanzi, J. M. ; Langley, S. J. ; [et al.]

Springer

European journal of clinical pharmacology 46 (1994), S. 167-171

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ISSN: 1432-1041

Keywords: Ranitidine ; Renal impairment ; pharmacokinetics

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Abstract This open study evaluated the influence of renal function on the pharmacokinetics of ranitidine (50 mg iv infusion given over 6 min). Five groups, each of 8 subjects, 1 with normal renal function and 4 with different degrees of renal impairment were studied. Renal function was assessed in each patient by 51Cr-EDTA (glomerular filtration rate, GFR), creatinine clearance (GFR) and N-methylnicotinamide clearance (reflecting glomerular and tubular function). Sixteen blood samples (5 ml) taken up to 48 h post dose from each subject were analysed for plasma ranitidine concentrations by reversed phase HPLC. Patient groups with renal impairment had significantly increased AUC∞ and t1/2 with corresponding decreases in CLp and λz when compared with normal subjects. There was also a significant increase in tmax but not in Cmax. There was a high linear correlation between the degree of renal impairment and ranitidine clearance. In patients with GFR ≤ 20 ml min−1, the AUC∞ mean ratio (compared with normal subjects) was up to 4.6 while for patients with GFR 20–50 ml min−1, the average AUC∞ ratio was 2.6. It is recommended that the dose of ranitidine is halved in patients with GFR ≤ 20 ml min−1.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00199883

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Application of the distance geometry algorithm to cyclic oligopeptide conformation searches (1990)

Peishoff, Catherine E. ; Dixon, J. Scott ; Kopple, Kenneth D.

New York : Wiley-Blackwell

Biopolymers 30 (1990), S. 45-56

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ISSN: 0006-3525

Keywords: Chemistry ; Polymer and Materials Science

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Chemistry and Pharmacology

Notes: The distance geometry algorithm as embodied in the program DGEOM was examined as a method for searching cyclic peptide conformations. Conformations were randomly generated using covalent distance and chirality constraints, but torsion angle rather than distance sampling was used for 1, 4 relationships. Structures so generated were energy minimized by a fixed number of iterations using the molecular mechanics program AMBER 3.0; electrostatic terms were excluded in the minimization. The effectiveness of this procedure in sampling conformational space for cyclic peptides was measured by the ability to recover, from a set of 500 structures, conformations similar to those experimentally observed for six cyclic peptides containing from 8 to 20 rotatable backbone bonds. Structures similar to experimental structures were recovered in a 16-bond case, but not for a 20-bond example. The method was also applied, with constraints on the peptide bond angles ω, to an additional example containing 21 ring bonds.

Additional Material: 5 Ill.