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Development of gingival overgrowth during daily long-term cyclosporine A treatment was studied in 2-yr-old beagles. Gingival enlargement developed in five of 12 dogs (42%), primarily in the mandibular anterior area. The earliest gingival changes occurred by 3 wk as an increase in the size of the interdental papillae. The lesions progressively became more severe, in some cases obscuring portions of teeth by wk 6. The redundant tissue exhibited and increase in connective tissue components and an inflammatory infiltrate primarily of plasma cells. Severity of the overgrowth varied in responding animals; both incidence and severity were related to the CSA concentration in blood. The mean CSA blood levels of responders were significantly greater than nonresponders at wk 3, 6 and 10. Since beagles develop gingival overgrowth similar to humans, they provide an excellent model to investigate the roles of local and systemic factors in the induction of gingival overgrowth. [ABSTRACT FROM AUTHOR]

The pharmacokinetics and associated pharmacodynamics of nifedipine were studied at steady state in 12 patients with angina pectoris who were receiving nifedipine 10-40 mg tid. After dosing, serum nifedipine concentrations rose rapidly and decayed in a log-linear fashion. The mean (± SEM) maximum serum concentration (Cmax) after dose normalization, and the time to Cmax (tmax) were 115 ± 7 ng/mL and 0.72 ± 0.13 hr, respectively. The mean area under the plasma concentration-time curve per 10-mg dose was 304 ± 34 hr-ng/mL. The average elimination rate constant was 0.205 ± 0.016 hr, and the harmonic mean elimination half-life was 3.4 hr (range, 2.5-4.9 hr). Heart rate increased (5-6 beats/min, P < .05) from baseline for up to one hour after dose, while mean diastolic blood pressure decreased (6-15 mm Hg, P < .05) for up to four hours. Cardiac output was increased (1.1-2.8 L/min, P < .05), and calculated total systemic resistance (3.6-6.3 mm Hg/L/min, P < .05) was decreased for the entire dosing interval after nifedipine dosing. Hysteresis plots for heart rate and mean diastolic blood pressure showed a time lag between changes in serum nifedipine concentrations and heart rate, but not between serum nifedipine concentrations and blood pressure. Changes in cardiac output did not correlate with serum nifedipine concentrations. The steady-state kinetic and dynamic parameter values in patients with angina pectoris in this study were similar to those found in healthy volunteers or hypertensive patients after acute nifedipine administration. Interpatient variability in pharmacokinetics and hemodynamic responses to nifedipine, rather than the underlying cardiovascular disease, would require titration of nifedipine doses to patient response. [ABSTRACT FROM AUTHOR]