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Title: The significance of toxicological laboratory investigations for the diagnostics of acute olanzapine poisoning

Abstract:

Introduction. Olanzapine is an atypical antipsychotic of thienobenzodiazepine group, which is used in the treatment of schizophrenia, maniacal phase of bipolar disorder and other psychiatric diseases. Its multidirectional activity as an antagonist of D1-4, 5-HT2A, 5-HT1C, H1, α1 and M1-5 receptors, apart its therapeutic properties, results in different side effects and the rich symptomatology in cases of acute poisoning. The growing number of olanzapine poisonings requires supporting of toxicological diagnostics by the quantitative measurement of olanzapine serum concentration. Aims of the study. In the course of acute olanzapine poisoning: (1) to evaluate the frequency and the intensity of clinical symptoms; (2) to study the drug toxicokinetics; (3) to examine relations among olanzapine serum concentration or the other toxicokinetic parameters and the intensity of selective clinical symptoms, physiological parameters and laboratory abnormalities; (4) to estimate the impact of some demographic, individual and iatrogenic factors on olanzapine serum concentration. Material. 26 adult patients (11 men and 13 women) hospitalized in the Toxicology Clinic in Krakow and the 1st Clinic of Internal Diseases and Acute Poisonings in Gdansk since 2005 to 2008 because of acute olanzapine poisoning. Methods. Data about the poisoning clinical course were extracted from medical records. The ; multiple serum samples for quantitative HPLC analysis of olanzapine were collected from each patient upon admission and after 6, 12, 18, 24, 30, 36, 42, 48, 60 and 72 h. Toxicokinetic modeling was performed according to population pharmacokinetic rules using NONMEM® version 7 and assuming the linear bicompartmental model for olanzapine. Statistical analysis was carried out with appropriate tools in STATISTICA version 9.0 PL. Results. The most common symptoms of acute olanzapine poisoning in the study group were: tachycardia (85%), psychomotor agitation (81%), hypertension (73%), miosis (65%) and coma with GCS<9 (54%). The medium values of toxicokinetic parameters were as follows (for abbreviations see the beginning of this thesis): D = 352,5 ± 220,0 mg; Cmax = 624,9 ± 634,4 ng/mL; tmax = 11,9 ± 8,1 h; Vss/F = 627,9 ± 232,6 L; Cl/F = 13,2 ± 10,2 L/h; AUC(0-∞) = 39,3 ± 40,5 mg•h/l; V1 = 47,6 ± 2,4 L and t½β = 53,1 ± 33,7 h. Statistical analysis revealed the following significant correlations: between Cmax and BRmin, TCOMA, Thosp; between AUC(0-∞) and BRmin, TCOMA, Thosp; between Cl/F and PUPØ, BILmax and between D and COMAGCS, COMAMat, BRmax, TEMPmax, PUPreac, TCOMA, TINT, Thosp. None of the operands SEX, AGE, BW, ALC, SMK, DEC and OLZ were found to have a significant influence on Cl/F or Vss/F, but some of them could wield such influence with p-value close to 0.05, namely, SMK ; , ALC and BW on Cl/F and ALC on Vss/F. Conclusions. In the acute olanzapine poisoning: (1) the most prevalent symptoms of poisoning come from circulatory and central nervous systems; (2) toxicokinetics has probably bicompartmental character and the concentration-time curve consists of two or three phases, often with double peaks; (3) D and Cmax are the best and complementary parameters for assessing the clinical course of poisoning, but TCOMA and Thosp correlates with toxicokinetic parameters in the best way; (4) toxicokinetic parameters may be influenced by: alcohol ingestion, smoking and body weight.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

toksykologia

Degree grantor:

Wydział Lekarski

Promoter:

Pach, Janusz

Date issued:

2010

Identifier:

oai:dl.cm-uj.krakow.pl:4728

Call number:

ZB-114711

Language:

pol

Access rights:

tylko w bibliotece

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Jun 3, 2022

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Jun 3, 2022

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