Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects

1988 ◽  
Vol 35 (1) ◽  
pp. 69-75 ◽  
Author(s):  
P. Harper ◽  
C. -E. Elwin ◽  
G. Cederblad
Keyword(s):  
Healthy Subjects ◽  
Oral Doses

Safety and pharmacokinetics of mifentidine after increasing oral doses in healthy subjects

1988 ◽  
Vol 35 (6) ◽  
pp. 673-676
Author(s):  
B. P. Imbimbo ◽  
M. Seiberling ◽  
U. Peuckert ◽  
G. Hoexter ◽  
H. Maier-Lenz ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Oral Doses

Tolerance and pilot pharmacokinetics of amiflamine after increasing single oral doses in healthy subjects

1986 ◽  
Vol 40 (1) ◽  
pp. 81-85 ◽  
Author(s):  
G Alván ◽  
C Graffner ◽  
M Grind ◽  
L L Gustafsson ◽  
J E Lindgren ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Oral Doses

Effect of dihydroergocristine administration on serum prolactin and growth hormone levels in normal, hyperprolactinaemic, and acromegalic subjects: further evidence for pituitary dopamine deficiency in these conditions

1983 ◽  
Vol 103 (1) ◽  
pp. 1-6 ◽  
Author(s):  
C. Ferrari ◽  
M. Romussi ◽  
R. Benco ◽  
P. Rampini ◽  
F. Mailland
Keyword(s):  
Growth Hormone ◽  
Healthy Subjects ◽  
Normal Subjects ◽  
Serum Prolactin ◽  
Pharmacological Properties ◽  
Healthy Controls ◽  
Oral Doses ◽  
Resumption Of Menses ◽  
Lowering Activity

Abstract. To evaluate further the pharmacological properties of dihydroergocristine in vivo, this drug (6 mg) or a placebo were administered orally on separate days to 11 healthy controls, 11 patients with adenomatous (n = 4) or idiopathic hyperprolactinaemia (n = 7), and 5 acromegalics with raised serum prolactin levels; serum prolactin (Prl) and growth hormone (GH) were measured at hourly intervals for 6 h. Dihydroergocristine induced a significant Prl decrease versus placebo in hyperprolactinaemics and acromegalics, but had no effect in healthy subjects. GH levels did not change in normals and hyperprolactinaemics, but decreased significantly in acromegalics. The Prl decrease induced by dihydroergocristine was significantly lower than that induced by l-dopa (500 mg po) in 9 hyperprolactinaemics so tested. Nomifensine (200 mg po) administered to 7 hyperprolactinaemics had no effect. Similarly, the GH decrease induced by the drug in acromegalics was significantly lower than that exerted by l-dopa, while nomifensine had no effect. Five hyperprolactinaemic patients were also given 12–18 mg dihydroergocristine daily for 3 months. There was evidence of partial or total Prl suppression and resumption of menses in all patients. These data indicate that dihydroergocristine is a relatively weak dopamine agonist at pituitary level and that oral doses, insufficient to exert Prl-lowering activity in normal subjects, are able to inhibit Prl and GH release in hyperprolactinaemics and dopamine-responsive acromegalics. These findings further support the existence of a 'denervation' supersensitivity to dopamine in these conditions, in which dopamine deficiency at pituitary level has been suggested on the basis of other experiments.

Safety, Pharmacokinetics, and Pharmacodynamics of CHF 3381, a Novel N-Methyl-D-Aspartate Antagonist, after Single Oral Doses in Healthy Subjects

2003 ◽  
Vol 43 (8) ◽  
pp. 901-911 ◽  
Author(s):  
Antoine Tarral ◽  
Philippe Dostert ◽  
Yann Guillevic ◽  
Laura Fabbri ◽  
Ivano Rondelli ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Oral Doses

scholarly journals First-in-human study to assess the safety, pharmacokinetics and pharmacodynamics of BMS-986177/JNJ-70033093, a direct, reversible, small molecule Factor XIa inhibitor in healthy volunteers

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Perera ◽  
Z Wang ◽  
J Luettgen ◽  
J Wang ◽  
D Li ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Healthy Volunteers ◽  
Small Molecule ◽  
Healthy Subjects ◽  
Funding Source ◽  
Private Company ◽  
Factor Xia ◽  
Clinically Significant ◽  
Oral Doses ◽  
The Impact

Abstract Background Inhibition of Factor XIa (FXIa) may provide a novel mechanism for systemic anticoagulation without increasing the risk of clinically significant bleeding in many conditions predisposing to a high risk of thrombotic or bleeding events. BMS-986177/JNJ-70033093 (BMS-177/JNJ-3093) is a small molecule that inhibits FXIa with high affinity and selectivity. Depending on the indication, BMS-177/JNJ-3093 may provide benefit to patients as add-on therapy to current standard of care (SOC) antithrombotic agents or potentially as a replacement for current SOC. Purpose To assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple oral doses of BMS-177/JNJ-3093 in healthy subjects. Methods This was a 2-part, randomized, double-blind, placebo-controlled, sequential single- (Part A) and multiple- (Part B) ascending dose study to assess the safety, tolerability, PK, and PD of BMS-177/JNJ-3093 in healthy subjects. In Part A (SAD) of the study, 48 subjects were treated in 6 panels (8 subjects per panel). The 200 mg and 500 mg dose panels investigated the impact of a high fat diet on PK. In Part B (MAD), 56 subjects were treated in 7 panels (8 subjects per panel) on a once daily (QD) or twice daily (BID) regimen for a 14-day period. Within each panel in Parts A and B, subjects were randomized to receive either BMS-177/JNJ-3093 or matched placebo (3:1). Results Administration of single ascending doses of BMS-177/JNJ-3093 up to 500 mg and multiple ascending doses of BMS-177/JNJ-3093 up to 200 mg BID or 500 mg QD for 14 days were safe and well tolerated. No subjects had a clinically significant bleeding event. All treatment-emergent adverse events were mild in severity. After single doses of BMS-177/JNJ-3093 ranging from 4 to 500 mg in fasted status, BMS-177/JNJ-3093 plasma concentration reached Cmax at 3 h postdose in all panels, indicating a similar rate of absorption. The terminal half-life ranged from 8.26 to 13.8 h across SAD panels. Over 20 to 200 mg, a dose proportional increase was observed; however, saturable absorption was seen at higher doses of 300 and 500 mg. Food also increased the bioavailability of BMS-177/JNJ-3093. In the MAD portion of the study, based on visual inspection of trough plasma concentration profiles, BMS-177/JNJ-3093 plasma concentration steady state was reached between 1–3 dosing days (ie, Days 2–4) for the QD panels and 6 dosing days (ie, Day 7) for the 200 mg BID panel. Renal excretion was relatively low, ranging from 8–20%. After single oral dose or multiple oral doses, there is a clear trend that aPTT was prolonged and the magnitude of change was related to drug exposure. Conclusion BMS-177/JNJ-3093 was safe and well tolerated in healthy volunteers. The PK and PD profile demonstrates suitable dosing properties for further clinical studies. Currently, two Phase II studies are ongoing. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This work was sponsored by Bristol-Myers Squibb and Janssen Research & Development, LLC

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