Comparison of metabolomics and platelet aggregometry between Plavix and generic clopidogrel in cats: a pilot study

2018 ◽  
Vol 21 (10) ◽  
pp. 951-958
Author(s):  
Mays Malkawi ◽  
Andrew D Woolcock ◽  
Pamela M Lee ◽  
Michael H Court ◽  
George E Moore ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Pilot Study ◽  
Carboxylic Acid ◽  
Active Metabolite ◽  
Plasma Concentrations ◽  
Parent Drug ◽  
Adenosine Diphosphate ◽  
Double Blind Study ◽  
Double Blind ◽  
Platelet Aggregometry

Objectives This pilot study sought to assess the metabolism of Plavix (Bristol-Myers Squibb/Sanofi) and generic clopidogrel in cats, using a novel assay for the measurement of clopidogrel, clopidogrel carboxylic acid (CCA) and clopidogrel active metabolite (CAM-D). Methods This was a prospective, randomized, double-blind study. Four healthy, skeletally mature cats were enrolled into the study. There were two treatment phases during which cats received either Plavix or generic clopidogrel at a dosage of 18.75 mg PO q24h for 7 days with a 2 week washout between phases. During each phase, plasma concentrations of parent drug and active and inactive metabolites were measured along with impedance platelet aggregometry in response to adenosine diphosphate (ADP). Results The ratio of CAM-D between generic clopidogrel and Plavix was 0.83 (equivalence reference 1.00, 90% confidence interval 0.80–1.25). Inhibition of ADP-induced platelet aggregation was variable, with two cats classified as non-responders in both treatment phases. The concentrations of CAM-D were not predictive of aggregometry-based responsiveness to either formulation of clopidogrel. Conclusions and relevance This is the first study comparing Plavix and generic clopidogrel in cats. Administration of the generic formulation resulted in comparable plasma concentrations of clopidogrel active metabolite when compared with Plavix.

The Effect of Warfarin Sodium on the Duration of Platelet Aggregation

1967 ◽  
Vol 18 (03/04) ◽  
pp. 766-778 ◽  
Author(s):  
H. J Knieriem ◽  
A. B Chandler
Keyword(s):  
Platelet Count ◽  
Placebo Group ◽  
Platelet Aggregation ◽  
Prothrombin Time ◽  
Platelet Rich Plasma ◽  
Healthy Adults ◽  
Double Blind Study ◽  
Double Blind ◽  
Warfarin Sodium

SummaryThe effect of the administration of warfarin sodium (Coumadin®) on the duration of platelet aggregation in vitro was studied. Coumadin was given for 4 consecutive days to 10 healthy adults who were followed over a period of 9 days. The duration of adenosine diphosphate-induced platelet aggregation in platelet-rich plasma, the prothrombin time, and the platelet count of platelet-rich plasma were measured. Four other healthy adults received placebos and participated in a double-blind study with those receiving Coumadin.Although administration of Coumadin caused a prolongation of the prothrombin time to 2 or 21/2 times the normal value, a decrease in the duration of platelet aggregation was not observed. In most individuals who received Coumadin an increase in the duration of platelet aggregation occurred. The effect of Coumadin on platelet aggregation was not consistently related to the prothrombin time or to the platelet count. In the placebo group there was a distinct relation between the duration of platelet aggregation and the platelet count in platelet-rich plasma.The mean increase in the duration of platelet aggregation when compared to the control value before medication with Coumadin was 37.7%. In the placebo group there was a mean increase of 8.4%. The difference between the two groups is significant (p <0.001). Increased duration of platelet aggregation also occurred in two individuals who received Coumadin over a period of 10 and 16 days respectively.

INITIAL STUDIES IN MAN WITH A NOVEL THROMBOXANE RECEPTOR BLOCKING DRUG GR32191

1987 ◽  
Author(s):  
M Thomas ◽  
P Lumley ◽  
P Ballard ◽  
J R O'Brien
Keyword(s):  
Platelet Aggregation ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Plasma Concentrations ◽  
Blocking Drug ◽  
Double Blind ◽  
Receptor Blocking ◽  
Thromboxane Receptor ◽  
Pre Treatment ◽  
Induced Aggregation

In-vitro GR32191 is a potent and specific thromboxane receptor blocking drug on platelets, and vascular and airways smooth muscle (Lumley et al this meeting). We have undertaken studies in healthy male subjects (n) to examine the effects of oral GR32191 upon platelet aggregation ex-vivo and template bleeding time. Platelet aggregation was monitored in whole blood by counting platelets electronically. Concentration-effect curves to U-46619 and ADP were constructed prior to and following drug or placebo. The degree of rightward displacement of a curve due to treatment was expressed as a concentration-ratio (CR) which was calculated at the 50% aggregation level (ECso post-treatment ECso pre-treatment). Plasma concentrations of GR32191 were determined by h.p.l.c. After single doses of GR32191 mean peak CR's of 8 and 80 were achieved with 0.125 and 0.25mg/kg (n=4) and values of 74 and 234 with 0.5 and lmg/kg (n=4). Peak effects were seen within 2 hours of dosing while activity was still present between 8 and 24 hours. ADP-induced aggregation was unaffected by drug (CR<2) and placebo was without significant effect upon the sensitivity to either aggregating agent (CR<2). GR32191 was rapidly absorbed and the plasma elimination half-life was about 2 hours. GR32191 17.5mg 12-hourly for 10 days (n=6) produced a progressive antagonism of U-46619 induced aggregation which resulted in a large continuous blockade in all subjects (range of 12htrough CR's 85 to 287). However, plasma concentrations of GR32191 did not accumulate on repeated administration. In a double-blind, placebo-controlled, cross-over study (n=16), a statistically significant (p= 0.002) increase in bleeding time was seen following treatment with GR32191 40mg twice daily for 7 days (pre-treatment mean 3.79 min, post-placebo mean 3.47 min, post-GR32191 mean 5.42 min). Rectal bleeding (n=l) has occurred with GR32191 but otherwise tolerability has been good. No drug related changes have been seen in routine laboratory safety screens. Clinical studies are in progress.

scholarly journals Antiplatelet effects of citalopram in patients with ischaemic stroke: A randomized, placebo-controlled, double-blind study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kristian Lundsgaard Kraglund ◽  
Janne Kaergaard Mortensen ◽  
Søren Paaske Johnsen ◽  
Grethe Andersen ◽  
Erik Lerkevang Grove
Keyword(s):  
Platelet Aggregation ◽  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Platelet Reactivity ◽  
Significant Inhibition ◽  
Controlled Study ◽  
Double Blind Study ◽  
Stroke Patients ◽  
Double Blind ◽  
Ssri Treatment

AbstractWe evaluated the effect of SSRI treatment on platelet aggregation in patients with ischaemic stroke and included patients from the randomized double-blind controlled study of citalopram in acute ischaemic stroke (TALOS). Patients on clopidogrel were included 6 months after acute ischaemic stroke. Platelet parameters, including P2Y12 platelet reactivity using the VerifyNow System, were measured at the last day of study treatment and repeated after a 14-day wash-out period. A total of 60 patients were included (n = 32 randomized to citalopram). Platelet aggregation levels did not differ between the citalopram group (mean 116, 95% CI 89 to 143) and the placebo group (mean 136, 95% CI 109 to 163) (On-treatment, p = 0.14). Similarly, there was no significant change in platelet aggregation in the citalopram group from on-treatment to post-treatment (mean difference 2.0; 95% CI −18 to 14). Platelet count, size and turnover were not affected by SSRI treatment. In conclusion, SSRI therapy did not lead to statistically significant inhibition of platelet aggregation in ischaemic stroke patients treated with clopidogrel.

Citric Acid Enhances the Antithrombotic Effect of Aspirin in Many Aspirin-Resistant Subjects

1997 ◽  
Vol 3 (1) ◽  
pp. 54-57 ◽  
Author(s):  
Svetlana Kaplan ◽  
Alexander Kaplan ◽  
Karen F. Marcoe ◽  
William P. Hammond ◽  
Lloyd D. Fisher ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Citric Acid ◽  
Poor Response ◽  
Inhibitory Effect ◽  
Consecutive Series ◽  
Double Blind ◽  
Platelet Aggregometry ◽  
Antithrombotic Medication ◽  
Average Drop ◽  
Apparently Healthy

This study had three objectives: (1) to determine the frequency of high platelet aggregators in a consecutive series of 268 apparently healthy volunteers who presented to our Center; (2) to assess the inhibitory effect of aspirin (ASA) on these high aggregators; (3) to determine, in a double-blind trial, whether or not the addition of citric acid (CTA) to ASA would increase its inhibitory effect in subjects who had a suboptimal response to aspirin alone. A platelet aggregation-scoring methodology developed for turbidimetric platelet aggregometry was used to quantify baseline aggregation and medicinal effects. We define a high aggregator as one whose unmedicated PA score is ≥30. We define the response of a high aggregator to ASA as poor if the medicated PA score stays at ≥30. We found that 58 of 268 apparently healthy unmedicated volunteers (22%) had PA scores ≥30. and that 27 of these (47%) had a poor response to 325 mg ASA, with an average drop in their PA scores from 49.5 ± 13.1 to 41.1 ± 8.6 (16%). Twenty-five of these 27 people were enrolled in the double-Mind study comparing the effect of ASA and ASA + CTA on platelet aggregability. Of these high aggregators who had a poor response to ASA, 12 of 25 (50%) had a good response to 162.5 mg of ASA plus 162.5 mg of CTA, with an average drop of their PA scores from 46.7 ± 13.2 to 22.0 ± 5.2 (53%). CTA alone had no effect on the PA score, which was similar to the control placebo. Our data suggest that a 1:1 combination of ASA and CTA may offer significantly greater protection agairtst arterial thrombotic events than ASA alone in subjects who respond poorly to ASA. Key Words: Platelet aggregation—Antithrombotic medication—Thrombosis.

Therapeutic Effect of Ticlopidine, a New Inhibitor of Platelet Aggregation, on Chronic Arterial Occlusive Diseases, a Double-blind Study versus Placebo

Angiology ◽  
1982 ◽  
Vol 33 (6) ◽  
pp. 357-367 ◽  
Author(s):  
Tatsuki Katsumura ◽  
Yoshio Mishima ◽  
Kisaku Kamiya ◽  
Shukichi Sakaguchi ◽  
Tatsuzo Tanabe ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Therapeutic Effect ◽  
Blind Study ◽  
Double Blind Study ◽  
Double Blind ◽  
Arterial Occlusive Diseases

Temelastine, a New H1-Receptor Antagonist

1986 ◽  
Vol 14 (4) ◽  
pp. 200-204 ◽  
Author(s):  
Fred Alexander ◽  
Robert M Stote ◽  
Nancy Allison ◽  
Robert G Familiar ◽  
Dianne Tatoian ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Plasma Concentrations ◽  
Controlled Study ◽  
Blood Levels ◽  
Double Blind Study ◽  
Double Blind ◽  
The Central Nervous System ◽  
H1 Receptor Antagonist ◽  
Oral Doses ◽  
Wheal Size

Temelastine is a selective, competitive histamine H1-receptor antagonist which does not penetrate the central nervous system. The effect of varying doses of temelastine was compared in a randomized, double-blind, controlled study by measuring the inhibition of cutaneous histamine wheals. In twelve subjects single oral doses of 50, 100 and 200 mg of temelastine produced dose-dependent reductions in wheal areas. The inhibition of wheal size was maximal by 2 hr after dosing and was present at 8 hr. At 2 hr the 50, 100, and 200 mg doses reduced the wheal size by 53, 64, and 78%, respectively. Chlorpheniramine, 4 mg, reduced wheal size by 32% at the same period. The ability of temelastine to antagonize the histamine-induced skin reaction over 20 hr was evaluated in a second randomized, double-blind study. Eight subjects participated. Temelastine, 100 mg, produced reductions of 64, 49, 56 and 51% in histamine wheal area at 8, 12, 16 and 20 hr, respectively. Plasma concentrations at these times were 4.04, 2.77, 1.88, and 1.44 μmol/l, respectively. These data suggest that blood levels as low as 1.44 μmol/l may be sufficient to produce an antihistaminic effect, and that daily or twice daily dosing with 100 mg may be adequate to control allergic symptoms.

Prophylactic treatment of irinotecan-induced diarrhea with neomycin (a randomized, placebo-controlled, double-blind study)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3626-3626
Author(s):  
R. H. Mathijssen ◽  
F. A. De Jong ◽  
D. F. Kehrer ◽  
R. H. Van Schaik ◽  
J. Verweij ◽  
...  
Keyword(s):  
Prophylactic Treatment ◽  
Plasma Concentrations ◽  
Aminoglycoside Antibiotic ◽  
Concomitant Administration ◽  
Patient Characteristics ◽  
Common Side Effect ◽  
Double Blind Study ◽  
Double Blind ◽  
Severe Diarrhea ◽  
Grade 3

3626 Background: Delayed-type diarrhea is a common side-effect of irinotecan, and is associated with a bacterial-mediated formation of the active irinotecan metabolite SN-38 from its glucuronide conjugate in the intestines. We hypothesized that concomitant administration of the aminoglycoside antibiotic neomycin would diminish exposure of the gut to SN-38, ameliorating the incidence of diarrhea. Methods: Patients were treated with irinotecan in a randomized, placebo-controlled, double-blind trial. In arm A, patients received irinotecan (350 mg/m2 i.v. for 90 minutes once every 3 weeks) combined with neomycin (660 mg orally 3 times daily for 3 consecutive days, starting 2 days before chemotherapy). In arm B, patients received the same irinotecan regimen with placebo. To detect a 50% reduction to less than grade 2 diarrhea (power=.80; P=.05), 60 patients had to be studied. Blood samples for additional pharmacokinetic and pharmacogenetic analyses were obtained after separate informed consent. Results: Sixty-two patients were evaluable for toxicity analysis. Relevant baseline patient characteristics (P>.06), SN-38 plasma concentrations (P=.80; N=43), and UGT1A1*28 genotype status (P=.58; N=52) were similar in both arms. Distribution, severity, and duration of diarrhea did not differ significantly between both arms (P>.32), although grade 3 diarrhea tended to be less frequent in the neomycin arm (45% reduction; P=.19). Grade 2 nausea was more common in this arm (39% vs. 9%; P<.01). The presence of at least one UGT1A1*28 allele was strongly related to the incidence of grade 2–3 diarrhea (69% vs. 34%; P=.01). Conclusions: Our results do not suggest a role for neomycin in the prophylactic treatment of irinotecan-induced diarrhea. In addition, neomycin does not influence systemic SN-38 pharmacokinetics. Also, it is suggested that each patient’s UGT1A1*28 genotype status could be used as a prospective screening tool to prevent severe diarrhea. No significant financial relationships to disclose.

Hydroxocobalamin, A Nitric Oxide Scavenger, in the Prophylaxis of Migraine: an Open, Pilot Study

Cephalalgia ◽  
2002 ◽  
Vol 22 (7) ◽  
pp. 513-519 ◽  
Author(s):  
P-HM van der Kuy ◽  
FWHM Merkus ◽  
JJHM Lohman ◽  
JWM ter Berg ◽  
PM Hooymans
Keyword(s):  
Nitric Oxide ◽  
Pilot Study ◽  
Migraine Attack ◽  
Acute Treatment ◽  
Total Duration ◽  
Double Blind Study ◽  
Prophylactic Effect ◽  
Attack Frequency ◽  
Double Blind ◽  
Total Study Population

Drugs which directly counteract nitric oxide (NO), such as endothelial receptor blockers, NO-synthase inhibitors, and NO-scavengers, may be effective in the acute treatment of migraine, but are also likely to be effective in migraine prophylaxis. In the underlying pilot study the prophylactic effect of the NO scavenger hydroxocobalamin after intranasal administration in migraine was evaluated. Twenty patients, with a history of migraine of <1 year and with two to eight migraine attacks per month, were included in an open trial. A baseline period was followed by an active treatment period of 3 months with 1 mg intranasal hydroxocobalamin daily. Patients were instructed to complete a diary in which details of each attack were described. A reduction in migraine attack frequency of ≥50% was seen in 10 of 19 patients, which corresponds to 53% of the patients (responders). A reduction of ≥30% was noted in 63% of the patients. The mean attack frequency in the total study population showed a reduction from 4.7 ± 1.7 attacks per month to 2.7 ± 1.6 ( P< 0.001). For the responders the migraine attack frequency was reduced from 5.2 ± 1.9 (baseline) to 1.9 ± 1.3 attacks per month ( P < 0.005), while for those who did not respond a non-significant reduction was found: 4.1 ± 1.4 to 3.7 ± 1.5 (P > 0.1). A reduction was also observed for the total duration of the migraine attacks per month, the total number of migraine days per month and the number of medication doses for acute treatment used per month. This is the first prospective, open study indicating that intranasal hydroxocobalamin may have a prophylactic effect in migraine. As a percentage of responders in prophylactic trials of > 35-40% is unlikely to be a placebo effect, a double-blind study is warranted.

scholarly journals Comparative bioavailability of two oral formulations of clopidogrel: Determination of clopidogrel and its carboxylic acid metabolite (SR26334) under fasting and fed conditions in healthy subjects

2014 ◽  
Vol 64 (1) ◽  
pp. 45-62 ◽  
Author(s):  
Nina Brvar ◽  
Sylvain Lachance ◽  
Ann Lévesque ◽  
Marjanca Breznik ◽  
Lea Cvitkovič Marčič ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Plasma Concentrations ◽  
Parent Drug ◽  
Oral Formulations ◽  
Period 2 ◽  
Crossover Studies ◽  
Inactive Metabolite ◽  
Acceptance Range ◽  
Effect Of Food ◽  
Comparative Bioavailability

Abstract Two randomized, single dose, 2-period, 2-sequence crossover studies were conducted to evaluate the comparative bioavailability of two clopidogrel formulations under fasting and fed conditions. Assessment of bioequivalence was based upon measurement of plasma concentrations of the parent drug, clopidogrel, and its major (inactive) metabolite, clopidogrel carboxylic acid, using improved methanol-free extraction. Bioequivalence of Krka’s formulation to the innovator’s formulation was demonstrated under both fasting and fed conditions on 205 volunteers. Confidence intervals for AUC0-t, AUC0-inf and Cmax of clopidogrel and its main metabolite were well within the acceptance range of 80.00 to 125.00 %. Food substantially increased the bioavailability of clopidogrel from both formulations, while no effect of food on the extent and rate of exposure to the metabolite was observed. The effect of food was comparable between the two formulations, as indicated by the same direction and rank of food impact on the bioavailability of both formulations.

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