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  • 1
    Electronic Resource
    Electronic Resource
    Ex vivo assays demonstrate potency and selectivity of the COX-2 inhibitor DFP after single dose administration (1999)
    Springer
    Inflammation research 48 (1999), S. 130-131 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000110050552
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  • 2
    Electronic Resource
    Electronic Resource
    Kinetics of cotinine after oral and intravenous administration to man (1987)
    Springer
    European journal of clinical pharmacology 31 (1987), S. 583-588 
    Details
    ISSN: 1432-1041
    Keywords: cotinine ; pharmacokinetics ; non-smokers ; absolute bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cotinine, the main metabolite of nicotine, was administered intravenously to healthy male non-smoking volunteers in doses of 5, 10 and 20 mg, and orally in doses of 10 and 20 mg. Intravenous administration was characterized by a dose-independent half-life of 12.2 h, mean residence time of 15.9 h, total clearance of 3.64 l h−1 and a volume of distribution of 56.5 l. Renal clearance was 0.46 l h−1 and approximately 12.0% of the dose was excreted unchanged in the urine. The mean absorption time after oral dosing ranged between 1 and 3 h, the peak concentration was reached within 45 min and the mean elimination half-lives were 12.9 and 11.7 h, respectively, after the 10 and 20 mg doses. Systemic bioavailability ranged between 0.84 and 1.11 following 10 mg and between 0.97 and 1.03 following the 20 mg dose. Mean urinary recovery and renal clearance were almost identical with the values after iv administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606635
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  • 3
    Electronic Resource
    Electronic Resource
    Plasma concentrations and effect on testosterone metabolism after single doses of MK-0434, a steroid 5 alpha-reductase inhibitor, in healthy subjects (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 123-126 
    Details
    ISSN: 1432-1041
    Keywords: Steroid 5α-reductase inhibitor ; Testosterone metabolism ; MK-0434 ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract A four-period, two-panel, single-rising-dose study (0.1–100 mg) was conducted in healthy males to investigate the pharmacodynamics, tolerability and pharmacokinetics of MK-0434, a steroid 5α-reductase inhibitor. MK-0434 was associated with a significant reduction in dihydrotestosterone, which was maximal at 24 h and maintained through 48 h post treatment. The maximum reduction was approximately 50 % and occurred at all doses above 5 mg (10, 25, 50 and 100 mg). MK-0434 appeared to have no effect on serum testosterone at these single doses. Rising single doses of MK-0434 were associated with an increase in Cmax and AUC but the changes were less than proportional to dose, most likely due to nonlinear absorption. MK-0434 given in single doses up to 100 mg was without significant adverse effects in healthy male volunteers. In summary, MK-0434 is a well-tolerated, potent, orally active 5α-reductase inhibitor in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199874
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  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetic interaction between indomethacin and diflunisal (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 507-512 
    Details
    ISSN: 1432-1041
    Keywords: indomethacin ; diflunisal ; drug interaction ; glucuronidation ; pharmacokinetics ; faecal blood loss
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of treatment with diflunisal on the steady-state pharmacokinetics of indomethacin has been studied in 16 healthy volunteers. The steady-state plasma concentration and AUC of indomethacin were significantly increased two- to threefold during treatment with diflunisal and its total clearance and total volume of distribution were significantly decreased. The urinary recovery of total indomethacin (unchanged+glucuronides) was significantly lower during administration of diflunisal, whereas excretion of the indomethacin metabolites desmethylindomethacin and desbenzoylindomethacin and their glucuronides was not significantly altered. The results can be explained by selective inhibition of glucuronidation of unchanged indomethacin by diflunisal. The interaction appears clinically relevant as potentially dangerous side effects of indomethacin are related to its plasma concentration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558077
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  • 5
    Electronic Resource
    Electronic Resource
    Plasma drug profiles and tolerability of MK-571 (L-660,711), a leukotriene D4 receptor antagonist, in man (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 427-430 
    Details
    ISSN: 1432-1041
    Keywords: MK-571 ; LTD4 receptor antagonist ; tolerability ; plasma profiles ; enantiomer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the tolerability and plasma drug profiles of a leukotriene D4 receptor antagonist, MK-571, given intravenously and as an oral solution in two separate trials. Study I (i.v.) involved 2 panels of 6 healthy men in a double-blind, alternating, incrementally increasing dose study with single doses up to 1500 mg. There was good tolerability at all doses. Plasma was assayed stereospecifically by HPLC for the S(+) and R(−) enantiomers of MK-571. For each enantiomer AUC values increased more than proportionately with increasing dose, suggesting nonlinear kinetics. The S(+) enantiomer was cleared more rapidly than the R(−) enantiomer. The apparent initial volume of distribution was less than 101 for both enantiomers. Study II (oral) involved 18 healthy subjects in 3 parallel groups who took multiple oral doses of 100, 300, and 600 mg t. i. d. for 31 doses. MK-571 administration was well tolerated, with only mild to moderate gastrointestinal discomfort at the highest dose. Total MK-571 (plasma samples assayed nonstereoselectively) was rapidly absorbed after oral administration, reaching peak concentrations at 1–2 h. Mean 8 h AUC increased from dose 1 to dose 31 in all subjects at all doses, suggesting a modest extent of accumulation (about 50 %) of total MK-571 in plasma with a t. i. d. dosage regimen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02220621
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  • 6
    Electronic Resource
    Electronic Resource
    Dose-dependent kinetics of the enantiomers of MK-571, an LTD4-receptor antagonist (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 431-433 
    Details
    ISSN: 1432-1041
    Keywords: MK-571, LTD4-receptor antagonist ; MK-0679, L-668,018, pharmacokinetics, enantiomers, healthy volunteers, pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of the enantiomers of MK-571 (MK-0679 and L-668,018) following single i. v. doses of MK-571 (L-660,711) was studied in a three way cross-over study in 12 healthy male volunteers. Each volunteer received 75 mg, 300 mg and 600 mg i. v. doses of MK-571 at weekly intervals. The disposition of both enantiomers appeared dose-dependent, since the AUC increased disproportionately faster than the dose. The dose dependency was much more pronounced for L-668,018: its AUC increased 6-fold from the 75 to the 300 mg dose, 16-fold from 75 to 600 mg and 2.7 fold from 300 to 600 mg. For MK-0679, the corresponding increases in AUC were 4.8-, ll-, and 2.3 fold. Regardless of dose, the elimination of L-668,018 was more rapid than that of MK-0679. The disposition of MK-0679 needs to be investigated independently to detect any potential influence of L-668,018 on its disposition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02220622
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  • 7
    Electronic Resource
    Electronic Resource
    Interaction between furosemide and the converting enzyme inhibitor benazepril in healthy volunteers (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 465-468 
    Details
    ISSN: 1432-1041
    Keywords: benazepril ; furosemide ; converting enzyme inhibitor ; pharmacokinetics ; drug interaction ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single oral doses of 10 mg converting enzyme inhibitor benazepril (CGS 14824A) and 40 mg furosemide were administered to 12 healthy male volunteers either separately or concomitantly. The pharmacokinetic parameters of benazepril were not influenced by coadministration of furosemide. Urinary excretion of total furosemide was significantly reduced by 10 to 20% in the presence of benazepril. This effect was considered clinically insignificant. Erect blood pressure decreased and pulse rate increased only during concomitant treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01046703
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  • 8
    Electronic Resource
    Electronic Resource
    Moexipril does not alter the pharmacokinetics or pharmacodynamics of warfarin (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 291-293 
    Details
    ISSN: 1432-1041
    Keywords: Moexipril ; Warfarin ; pharmacokinetics ; pharmacodynamics ; drug-interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The potential effect of moexipril, a new converting enzyme inhibitor, on the pharmacokinetics and pharmacodynamics of a single dose of warfarin has been investigated. Ten healthy male volunteers received in a randomised crossover fashion a single oral dose of 50 mg warfarin sodium alone and together with the first dose of 6 days of oral treatment with moexipril 15 mg o.d. Mean oral plasma clearance of (R)-warfarin was 175 ml·h−1 in the absence and 181 ml·h−1 in the presence of moexipril, and the corresponding values for (S)-warfarin were 248 ml·h−1 and 249 ml·h−1. Apparent volume of distribution, peak plasma concentration, time to reach peak concentration and area under the plasma concentration-time curve both of (R)- and (S)-warfarin were not significantly affected. Moexipril did not alter the maximum prothrombin time (20.3 versus 20.1 s, respectively in the absence and presence of moexipril), time to maximum response (48.0 versus 50 h) and area under the prothrombin time versus time curve. The results suggest that a clinically important interaction between moexipril and warfarin is unlikely to occur in patients treated with both drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315400
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  • 9
    Electronic Resource
    Electronic Resource
    Effects of enteric-coated, low-dose aspirin on parameters of platelet function (2002)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 16 (2002), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Aspirin is widely used as an anti-thrombotic drug; however, it has been suggested that enteric-coated formulations of aspirin may be less bioavailable and less effective as anti-thrombotic agents.Aim : To assess the effect of a formulation of enteric-coated, low-dose (81 mg) aspirin on serum generated thromboxane B2 and platelet aggregation in healthy subjects.Methods : Twenty-four subjects participated in a double-blind, randomized, placebo-controlled, parallel-group, multiple-dose study. Twelve subjects in each of two groups received a daily oral dose of enteric-coated aspirin (81 mg) or matching placebo for 7 days. Serum thromboxane B2 and platelet aggregation (using 1 mm arachidonic acid and 1 µg/mL collagen as agonists) were measured 1–3 days prior to day 1, on day 1 (prior to therapy) and 4 h after the last dose on day 7.Results : After seven daily doses of enteric-coated aspirin, the mean percentage inhibition from baseline of ex vivo generated serum thromboxane B2 was 97.4%, compared with a 7.8% increase after placebo treatment. The mean percentage inhibition of arachidonic acid- and collagen-induced platelet aggregation was 97.9% and 70.9%, respectively, following enteric-coated aspirin, compared with − 1.0% and 2.7%, respectively, after placebo.Conclusions : The anti-platelet effects of multiple, daily, low-dose aspirin (as assessed by inhibition of serum thromboxane B2 and platelet aggregation) are not adversely affected by enteric coating.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2002.01332.x
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  • 10
    Electronic Resource
    Electronic Resource
    Hormonal effects, tolerability, and preliminary kinetics in men of MK-906, a 5α-reductase inhibitor
    Amsterdam : Elsevier
    Steroids 56 (1991), S. 469-471 
    Details
    ISSN: 0039-128X
    Keywords: 5α-reductase inhibitor ; Finasteride ; dihydrotestosterone ; human ; pharmacodynamics ; pharmacokinetics ; steroids ; testosterone
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0039-128X(91)90003-E
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