Single-dose and multiple-dose pharmacokinetics of etintidine in healthy volunteers

1988 ◽  
Vol 34 (1) ◽  
pp. 101-104 ◽  
Author(s):  
S. -M. Huang ◽  
T. B. Marriott ◽  
H. S. Weintraub ◽  
J. D. Arnold ◽  
J. Boccagno ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Multiple Dose ◽  
Multiple Dose Pharmacokinetics

Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum

2016 ◽  
pp. ntw211
Author(s):  
Anna Hansson ◽  
Thomas Rasmussen ◽  
Holger Kraiczi
Keyword(s):  
Single Dose ◽  
Multiple Dose ◽  
Multiple Dose Pharmacokinetics

Single- and Multiple-dose Pharmacokinetics of Nefiracetam, a New Nootropic Agent, in Healthy Volunteers

1992 ◽  
Vol 44 (9) ◽  
pp. 750-754 ◽  
Author(s):  
Y. FUJIMAKI ◽  
K. SUDO ◽  
H. HAKUSUI ◽  
H. TACHIZAWA ◽  
M. MURASAKI
Keyword(s):  
Healthy Volunteers ◽  
Multiple Dose ◽  
Nootropic Agent ◽  
Multiple Dose Pharmacokinetics

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Anti-Vwf Nanobody® ALX-0681 After Single and Multiple Subcutaneous Administrations to Healthy Volunteers.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1063-1063 ◽  
Author(s):  
Khalid Abd-Elaziz ◽  
Pieter W. Kamphuisen ◽  
Christophe Lyssens ◽  
Mariska Reuvers ◽  
Izaak den Daas ◽  
...  
Keyword(s):  
Single Dose ◽  
Platelet Aggregation ◽  
Healthy Volunteers ◽  
Dose Level ◽  
Multiple Dose ◽  
Phase I Trial ◽  
Post Dose ◽  
Dose Cohort ◽  
Clinically Significant ◽  
Dose Levels

Abstract Abstract 1063 Poster Board I-85 ALX-0681 is a humanized bivalent Nanobody®, that binds to the A1 domain of von Willebrand factor (vWF) and hence blocks its interaction with platelet receptor GPIb-IX-V. Given its mode of action, ALX-0681 could provide an alternative treatment option for thrombotic thrombocytopenic purpura (TTP), a rare and life-threatening condition characterized by systemic platelet aggregation in the microcirculation mediated by activated vWF multimers. The goal of this Phase I trial in healthy volunteers was to determine the maximum tolerated dose (MTD) or biologically effective dose (BED) and the Phase II dosing and scheduling of ALX-0681, in order to support the further clinical development of ALX-0681 in TTP patients. In total, 36 healthy volunteers were included in this randomized, placebo-controlled study to evaluate the safety of single ascending doses and multiple doses of ALX-0681 administered subcutaneously (s.c.) (Table 1). Table 1 Dosing schedule for Phase I trial with ALX-0681 Cohort Dose (mg) Number of daily doses Subjects receiving ALX-0681 Subjects receiving placebo Single dose Cohort 1 2 1 3 1 Cohort 2 4 1 3 1 Cohort 3 8 1 3 1 Cohort 4 16 1 3 1 Cohort 5 10 1 3 1 Multiple dose Cohort 6 10 7 6 2 Cohort 7 10 14 6 2 Study endpoints included safety (dose limiting toxicities, adverse events (AEs) and immunogenicity), pharmacokinetics (PK), pharmacodynamics (PD) and pharmacological efficacy of ALX-0681. The latter endpoint was addressed by measuring the ristocetin cofactor (RICO) biomarker, reflecting vWF mediated inhibition of platelet aggregation. ALX-0681 was safe and well tolerated at all dose levels (Table 2). One unrelated SAE (meniscus lesion) occurred. The number of observed signs of bleeding and bruises increased with increasing treatment duration. However, all these events were of mild intensity. No signs of immunogenicity were observed for a minimum of 45 days after the last injection. Table 2 Summary of main safety results (number (%) of subjects with event) Dose level Subjects (n) AE SAE Bleeding Hematoma at injection site Hematoma at blood sampling site Other hematoma Single dose 2 mg 3 2 (67) 0 (0) 1 (33) 0 (0) 1 (33) 0 (0) 4 mg 3 2 (67) 0 (0) 1 (33) 0 (0) 0 (0) 0 (0) 8 mg 3 3 (100) 0 (0) 0 (0) 0 (0) 1 (33) 0 (0) 16 mg 3 3 (100) 0 (0) 0 (0) 0 (0) 0 (0) 1 (33) 10 mg 3 1 (33) 0 (0) 0 (0) 0 (0) 1 (33) 0 (0) Placebo 5 3 (60) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Multiple dose 10 mg (7d) 6 6 (100) 1 (17) 5 (83) 1 (17) 0 (0) 3 (50) Placebo (7d) 2 2 (100) 0 (0) 1 (50) 0 (0) 1 (50) 0 (0) 10 mg (14d) 6 6 (100) 0 (0) 5 (83) 5 (83) 4 (67) 5 (83) Placebo (14d) 2 2 (100) 0 (0) 1 (50) 0 (0) 0 (0) 0 (0) PK analysis showed a rapid increase in ALX-0681 plasma concentration (tmax = 4-10 h post dose), followed by a slow elimination phase (t1/2 = 10-78 h). All subjects dosed with ALX-0681 at 8 mg or higher showed complete inhibition of RICO activity to < 20% with an onset of 1-6 h post dose. This inhibition was maintained until 12-360 h post dose, depending on the dose level (Table 3). Overall, 20 (74%) and 17 (63%) of ALX-0681 treated subjects experienced a drop in vWF and FVIII levels below 50% of pre-dose levels, respectively. These events were all transient and not clinically significant. Table 3 Summary of main PD results (number (%) of subjects with event) Dose level Subjects (n) RICO < 20% vWF < 50% FVIII < 50% Subjects (%) Start (h)* Stop (h)* Single dose 2 mg 3 2 (67) 2-4 12-18 3 (100) 0 (0) 4 mg 3 2 (67) 4-6 18-36 1 (33) 1 (33) 8 mg 3 3 (100) 2-4 18-48 3 (100) 3 (100) 16 mg 3 3 (100) 1-4 48 0 (0) 2 (67) 10 mg 3 3 (100) 2-6 24-36 3 (100) 3 (100) Placebo 5 0 (0) NA NA 0 (0) 0 (0) Multiple dose 10 mg (7d) 6 6 (100) 2-4 168-192 5 (83) 3 (50) Placebo (7d) 2 0 (0) NA NA 0 (0) 0 (0) 10 mg (14d) 6 6 (100) 2-4 336-360 5 (83) 5 (83) Placebo (14d) 2 0 (0) NA NA 0 (0) 0 (0) * Time relative to first administration NA: not applicable In conclusion, ALX-0681 administered s.c. for up to 14 days was well tolerated and did not result in any clinically significant AEs. No local reactions, local intolerances or signs of clinically relevant bleeding were reported. The PD marker indicated complete inhibition of vWF mediated platelet aggregation following single daily s.c. injections of 10 mg, which was maintained over the 2 weeks treatment period. Multiple daily administration of s.c. injections of ALX-0681 did not result in an immunogenic reaction for a minimum of 45 days following completion of treatment. Based on the results of this study, ALX-0681 development will be advanced into a Phase II study in TTP patients to investigate the safety and efficacy of ALX-0681 in the target patient population. Disclosures: Abd-Elaziz: Ablynx NV: Consultancy. Kamphuisen:Ablynx NV: Consultancy. Lyssens:Ablynx NV: Employment. Reuvers:Ablynx NV: Consultancy. den Daas:Ablynx NV: Consultancy. Van Bockstaele:Ablynx NV: Employment. Vercruysse:Ablynx NV: Employment. Ulrichts:Ablynx NV: Employment. Baumeister:Ablynx NV: Employment. Crabbe:Ablynx NV: Employment. Compernolle:Ablynx NV: Employment. Holz:Ablynx NV: Employment.

Multiple dose pharmacokinetics of tiludronate in healthy volunteers

1996 ◽  
Vol 51 (2) ◽  
pp. 175-181 ◽  
Author(s):  
H. R. Schwietert ◽  
P. A. M. Peeters ◽  
J. Dingemanse ◽  
J. F. Thiercelin ◽  
J. Necciari ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Multiple Dose ◽  
Multiple Dose Pharmacokinetics

scholarly journals Single- and Multiple-Dose Pharmacokinetics of Caspofungin in Healthy Men

2002 ◽  
Vol 46 (3) ◽  
pp. 739-745 ◽  
Author(s):  
Julie A. Stone ◽  
Sherry D. Holland ◽  
Peter J. Wickersham ◽  
Andrew Sterrett ◽  
Michael Schwartz ◽  
...  
Keyword(s):  
Single Dose ◽  
Multiple Dose ◽  
Panel Study ◽  
Loading Dose ◽  
Plasma Drug ◽  
Single Dose Study ◽  
Healthy Men ◽  
Drug Concentrations ◽  
Multiple Dose Pharmacokinetics ◽  
Plasma Drug Concentrations

ABSTRACT Caspofungin, a glucan synthesis inhibitor, is being developed as a parenteral antifungal agent. The pharmacokinetics of caspofungin following 1-h intravenous infusions in healthy men was investigated in four phase I studies. In an alternating two-panel (six men each), rising-single-dose study, plasma drug concentrations increased proportionally with the dose following infusions of 5 to 100 mg. The β-phase half-life was 9 to 10 h. The plasma drug clearance rate averaged 10 to 12 ml/min. Renal clearance of unchanged drug was a minor pathway of elimination (∼2% of the dose). Multiple-dose pharmacokinetics were investigated in a 2-week, serial-panel (5 or 6 men per panel) study of doses of 15, 35, and 70 mg administered daily; a 3-week, single-panel (10 men) study of a dose of 70 mg administered daily; and a parallel panel study (8 men) of a dose of 50 mg administered daily with or without a 70-mg loading dose on day 1. Moderate accumulation was observed with daily dosing. The degree of drug accumulation and the time to steady state were somewhat dose dependent. Accumulation averaged 24% at 15 mg daily and ∼50% at 50 and 70 mg daily. Mean plasma drug concentrations were maintained above 1.0 μg/ml, a target selected to exceed the MIC at which 90% of the isolates of the most clinically relevant species of Candida were inhibited, throughout therapy with daily treatments of 70 or 50 mg plus the loading dose, while they fell below the target for the first 2 days of a daily treatment of 50 mg without the loading dose. Caspofungin infused intravenously as a single dose or as multiple doses was generally well tolerated. In conclusion, the pharmacokinetics of caspofungin supports the clinical evaluation of once-daily dosing regimens for efficacy against fungal infections.

scholarly journals Single-Dose and Multiple-Dose Pharmacokinetics and Dose Proportionality of Intravenous and Intramuscular HPβCD-Diclofenac (Dyloject) Compared with Other Diclofenac Formulations

2013 ◽  
Vol 33 (10) ◽  
pp. 1012-1021 ◽  
Author(s):  
Fred Mermelstein ◽  
Douglas A. Hamilton ◽  
Curtis Wright ◽  
Peter G. Lacouture ◽  
Atulkumar Ramaiya ◽  
...  
Keyword(s):  
Single Dose ◽  
Multiple Dose ◽  
Dose Proportionality ◽  
Multiple Dose Pharmacokinetics
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