Research Article
Effects of Paliperidone Palmitate on Coagulation:
An Experimental Study
Enver Demirel YJlmaz,
1
Sedat Motor,
2
Fatih Sefil,
3
Neslihan PJnar,
4
Hanifi Kokacya,
5
Mustafa Kisa,
6
and Suleyman Oktar
6
1
Department of Psychiatry, Faculty of Medicine, Bezmialem University, Istanbul, Turkey
2
Department of Biochemistry, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey
3
Department of Physiology, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey
4
Department of Pharmacology, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey
5
Department of Psychiatry, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey
6
Department of Pharmacology, Faculty of Medicine, Mevlana University, Konya, Turkey
Correspondence should be addressed to Suleyman Oktar; suleymanoktar@yahoo.com
Received 24 September 2013; Accepted 8 December 2013; Published 9 February 2014
Academic Editors: J. Csernansky and E. Ruther
Copyright © 2014 Enver Demirel Yılmaz et al. Tis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Objective. Te aim of the present study was to examine the efects of a new antipsychotic drug paliperidone palmitate on hemogram
and coagulation parameters in rats. Materials and Methods. Experiments were performed on 22 female albino Wistar rats (8–12
weeks old). Control group was given drinking water as vehicle (0.3mL). PAL-1 rats were given 1mg/kg paliperidone palmitate
(in 0.3mL drinking water) by oral gavage once a day for ten days and PAL-3 rats received 3mg/kg paliperidone palmitate (in
0.3mL drinking water) by oral gavage for ten days. Blood samples were drawn from the heart 24 hours afer the last drug dose,
and hemogram and coagulation parameters were measured with automated analyzers. Results. Hemogram did not change in the
paliperidone treated groups compared to the controls. Factor VIII levels decreased in the PAL-1 and PAL-3 groups; and this decrease
was signifcantly greater in the PAL-3. Factor IX levels decreased in PAL-3 rats, but its levels also increased in PAL-1 rats compared
to the control. Discussion. Paliperidone has led to changes in the serum levels of coagulation factors VIII and IX in rats. As a result,
paliperidone may be causing thromboembolism or bleeding in a dose-independent manner.
1. Introduction
Several studies showed the relationship between venous
thromboembolism and the use of antipsychotic drugs espe-
cially atypical agents [1]. Many clinical studies have pointed to
thrombogenic potential of atypical antipsychotic compounds
such as clozapine, risperidone, and olanzapine. Cerebrovas-
cular adverse events such as stroke and transient ischemic
attack were observed at a high rate in some clinical trials in
patients who received treatment with olanzapine or risperi-
done [2]. For example, the incidence of cerebrovascular
adverse events related to risperidone in elderly patients was
3.8%, compared with 1.5% placebo [3]. In a previous study, the
relationship between antipsychotic medications and treat-
ment of venous thromboembolism was strongly supported
by a large, nested case-control study [4]. Although several
hypotheses have been proposed, the biological mechanism
explaining this relationship is unknown. Drug-induced seda-
tion, obesity, hyperleptinemia, antiphospholipid antibodies,
and increased activity of the hemostatic system may be high
risk for thromboembolism [5].
Paliperidone (INVEGA, Ortho-McNeil-Janssen Pharma-
ceuticals, Inc., Titusville, NJ, USA) was approved by the FDA
for the treatment of schizophrenia in 2006. Paliperidone
palmitate, a long-acting atypical antipsychotic drug, is used
for adults for the treatment of schizophrenia. Paliperidone is
the 9-OH metabolite of risperidone and paliperidone palmi-
tate is also the palmitate ester of paliperidone. Paliperidone
palmitate belongs to the chemical class of benzisoxazole
derivatives [6]. Te precise mechanism of paliperidone is
Hindawi Publishing Corporation
e Scientific World Journal
Volume 2014, Article ID 964380, 5 pages
http://dx.doi.org/10.1155/2014/964380