Abstract
Eight healthy volunteers received a 5 min i.v. infusion of lysine theophylline, equivalent to 197 mg anhydrous theophylline, both before (day 1) and during (day 5) steady state chronic oral dosing with slow release nifedipine 20 mg 12 hourly. A theophylline pharmacokinetic profile was performed on day 1 and day 5 and a nifedipine pharmacokinetic profile was performed on day 4 and day 5. The greatest difference in serum theophylline concentrations was seen at the first sampling time (5 min after completion of the infusion) with a mean concentration of 9.9 mg l-1 during nifedipine administration and 14.6 mg l-1 with theophylline alone. Thereafter, the difference fell to approximately 1 mg l-1 until 6 h when they became almost identical. Repeated measures analysis of variance using the theophylline serum concentrations at each of ten time points over 8 h as the repeated measures showed a small but significant effect of nifedipine (F(1,151) = 7.0, P less than 0.01) on serum theophylline concentrations. Mean volume of distribution (V) rose from 0.33 +/- 0.07 to 0.39 +/- 0.06 1 kg-1 corrected body weight (CBW) in the presence of nifedipine (t = 2.23, P = 0.052). Theophylline clearance, area under the curve to 8 h AUC (0-8), area under the curve to infinity AUC (0-infinity) and elimination half-life (t1/2) did not change appreciably. No statistically significant changes in nifedipine pharmacokinetics occurred in the presence of theophylline.
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Selected References
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- Belz G. G., Aust P. E., Munkes R. Digoxin plasma concentrations and nifedipine. Lancet. 1981 Apr 11;1(8224):844–845. doi: 10.1016/s0140-6736(81)92727-6. [DOI] [PubMed] [Google Scholar]
- Chang J., Gotcher S., Gushaw J. B. Homogeneous enzyme immunoassay for theophylline in serum and plasma. Clin Chem. 1982 Feb;28(2):361–367. [PubMed] [Google Scholar]
- Debbas N. M., Jackson S. H., Shah K., Abrams S. M., Johnston A., Turner P. The bioavailability and pharmacokinetics of slow release nifedipine during chronic dosing in volunteers. Br J Clin Pharmacol. 1986 Apr;21(4):385–388. doi: 10.1111/j.1365-2125.1986.tb05211.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gal P., Jusko W. J., Yurchak A. M., Franklin B. A. Theophylline disposition in obesity. Clin Pharmacol Ther. 1978 Apr;23(4):438–444. doi: 10.1002/cpt1978234438. [DOI] [PubMed] [Google Scholar]
- Iliopoulou A., Aldhous M. E., Johnston A., Turner P. Pharmacokinetic interaction between theophylline and erythromycin. Br J Clin Pharmacol. 1982 Oct;14(4):495–499. doi: 10.1111/j.1365-2125.1982.tb02018.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnston A. SIMP: a computer program in BASIC for nonlinear curve fitting. J Pharmacol Methods. 1985 Dec;14(4):323–329. doi: 10.1016/0160-5402(85)90008-7. [DOI] [PubMed] [Google Scholar]
- Johnston A., Woollard R. C. STRIPE: an interactive computer program for the analysis of drug pharmacokinetics. J Pharmacol Methods. 1983 May;9(3):193–199. doi: 10.1016/0160-5402(83)90038-4. [DOI] [PubMed] [Google Scholar]
- Klein H. O., Lang R., Di Segni E., Kaplinsky E. Verapamil-digoxin interaction. N Engl J Med. 1980 Jul 17;303(3):160–160. doi: 10.1056/NEJM198007173030316. [DOI] [PubMed] [Google Scholar]
- Melethil S., Carlson J. D., Haug M. T. Predictability of theophylline levels. Drug Intell Clin Pharm. 1982 Sep;16(9):695–697. doi: 10.1177/106002808201600910. [DOI] [PubMed] [Google Scholar]
- Pedersen K. E., Dorph-Pedersen A., Hvidt S., Klitgaard N. A., Kjaer K., Nielsen-Kudsk F. Effect of nifedipine on digoxin kinetics in healthy subjects. Clin Pharmacol Ther. 1982 Nov;32(5):562–565. doi: 10.1038/clpt.1982.203. [DOI] [PubMed] [Google Scholar]
- Waller D. G., Renwick A. G., Gruchy B. S., George C. F. The first pass metabolism of nifedipine in man. Br J Clin Pharmacol. 1984 Dec;18(6):951–954. doi: 10.1111/j.1365-2125.1984.tb02569.x. [DOI] [PMC free article] [PubMed] [Google Scholar]