Abstract
Background: Liver disease (LD) prolongs mirtazapine half-life in humans, but it is unknown if this occurs in cats with LD and healthy cats. Hypothesis/Objectives: To determine pharmacokinetics of administered orally mirtazapine in vivo and in vitro (liver microsomes) in cats with LD and healthy cats. Animals: Eleven LD and 11 age-matched control cats. Methods: Case-control study. Serum was obtained 1 and 4 hours (22 cats) and 24 hours (14 cats) after oral administration of 1.88 mg mirtazapine. Mirtazapine concentrations were measured by liquid chromatography with tandem mass spectrometry. Drug exposure and half-life were predicted using limited sampling modeling and estimated using noncompartmental methods. in vitro mirtazapine pharmacokinetics were assessed using liver microsomes from 3 LD cats and 4 cats without LD. Results: There was a significant difference in time to maximum serum concentration between LD cats and control cats (median [range]: 4 [1-4] hours versus 1 [1-4] hours; P =.03). The calculated half-life of LD cats was significantly prolonged compared to controls (median [range]: 13.8 [7.9-61.4] hours versus 7.4 [6.7-9.1] hours; P <.002). Mirtazapine half-life was correlated with ALT (P =.002; r =.76), ALP (P <.0001; r =.89), and total bilirubin (P =.0008; r =.81). The rate of loss of mirtazapine was significantly different between microsomes of LD cats (–0.0022 min−1, CI: −0.0050 to 0.00054 min−1) and cats without LD (0.01849 min−1, CI: −0.025 to −0.012 min−1; P =.002). Conclusions and Clinical Importance: Cats with LD might require less frequent administration of mirtazapine than normal cats.
| Original language | English (US) |
|---|---|
| Journal | Journal of Veterinary Internal Medicine |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
| Externally published | Yes |
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Keywords
- appetite stimulant
- feline
- hepatic
- microsomes
ASJC Scopus subject areas
- veterinary(all)
Cite this
In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease. / Fitzpatrick, Rikki L.; Quimby, Jessica M.; Benson, Kellyi K.; Ramirez, Dominique; Sieberg, Liberty G.; Wittenburg, Luke Anthony; Gustafson, Daniel L.
In: Journal of Veterinary Internal Medicine, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease
AU - Fitzpatrick, Rikki L.
AU - Quimby, Jessica M.
AU - Benson, Kellyi K.
AU - Ramirez, Dominique
AU - Sieberg, Liberty G.
AU - Wittenburg, Luke Anthony
AU - Gustafson, Daniel L.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Background: Liver disease (LD) prolongs mirtazapine half-life in humans, but it is unknown if this occurs in cats with LD and healthy cats. Hypothesis/Objectives: To determine pharmacokinetics of administered orally mirtazapine in vivo and in vitro (liver microsomes) in cats with LD and healthy cats. Animals: Eleven LD and 11 age-matched control cats. Methods: Case-control study. Serum was obtained 1 and 4 hours (22 cats) and 24 hours (14 cats) after oral administration of 1.88 mg mirtazapine. Mirtazapine concentrations were measured by liquid chromatography with tandem mass spectrometry. Drug exposure and half-life were predicted using limited sampling modeling and estimated using noncompartmental methods. in vitro mirtazapine pharmacokinetics were assessed using liver microsomes from 3 LD cats and 4 cats without LD. Results: There was a significant difference in time to maximum serum concentration between LD cats and control cats (median [range]: 4 [1-4] hours versus 1 [1-4] hours; P =.03). The calculated half-life of LD cats was significantly prolonged compared to controls (median [range]: 13.8 [7.9-61.4] hours versus 7.4 [6.7-9.1] hours; P <.002). Mirtazapine half-life was correlated with ALT (P =.002; r =.76), ALP (P <.0001; r =.89), and total bilirubin (P =.0008; r =.81). The rate of loss of mirtazapine was significantly different between microsomes of LD cats (–0.0022 min−1, CI: −0.0050 to 0.00054 min−1) and cats without LD (0.01849 min−1, CI: −0.025 to −0.012 min−1; P =.002). Conclusions and Clinical Importance: Cats with LD might require less frequent administration of mirtazapine than normal cats.
AB - Background: Liver disease (LD) prolongs mirtazapine half-life in humans, but it is unknown if this occurs in cats with LD and healthy cats. Hypothesis/Objectives: To determine pharmacokinetics of administered orally mirtazapine in vivo and in vitro (liver microsomes) in cats with LD and healthy cats. Animals: Eleven LD and 11 age-matched control cats. Methods: Case-control study. Serum was obtained 1 and 4 hours (22 cats) and 24 hours (14 cats) after oral administration of 1.88 mg mirtazapine. Mirtazapine concentrations were measured by liquid chromatography with tandem mass spectrometry. Drug exposure and half-life were predicted using limited sampling modeling and estimated using noncompartmental methods. in vitro mirtazapine pharmacokinetics were assessed using liver microsomes from 3 LD cats and 4 cats without LD. Results: There was a significant difference in time to maximum serum concentration between LD cats and control cats (median [range]: 4 [1-4] hours versus 1 [1-4] hours; P =.03). The calculated half-life of LD cats was significantly prolonged compared to controls (median [range]: 13.8 [7.9-61.4] hours versus 7.4 [6.7-9.1] hours; P <.002). Mirtazapine half-life was correlated with ALT (P =.002; r =.76), ALP (P <.0001; r =.89), and total bilirubin (P =.0008; r =.81). The rate of loss of mirtazapine was significantly different between microsomes of LD cats (–0.0022 min−1, CI: −0.0050 to 0.00054 min−1) and cats without LD (0.01849 min−1, CI: −0.025 to −0.012 min−1; P =.002). Conclusions and Clinical Importance: Cats with LD might require less frequent administration of mirtazapine than normal cats.
KW - appetite stimulant
KW - feline
KW - hepatic
KW - microsomes
UR - http://www.scopus.com/inward/record.url?scp=85054719757&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054719757&partnerID=8YFLogxK
U2 - 10.1111/jvim.15237
DO - 10.1111/jvim.15237
M3 - Article
C2 - 30307637
AN - SCOPUS:85054719757
JO - Journal of Veterinary Internal Medicine
JF - Journal of Veterinary Internal Medicine
SN - 0891-6640
ER -