Objectives Measure drug exposure and clinic effects after administration of transdermal mirtazapine (TMZ) in healthy cats. Methods Phase I: Seven healthy research cats received A) 3.75 mg and 7.5 mg TMZ once aurally with 48 hour serum sampling (serum samples were obtained via jugular catheter at 0, 0.5, 1, 2, 5, 9, 12, 24, 36 and 48 h), B) 7.5 mg TMZ and placebo daily aurally for six days then 48 h serum sampling C) 1.88 mg mirtazapine orally once with serum sampling at 1, 4 and 8 h. Phase II: Twenty client-owned cats were enrolled in a randomized double-blind placebo-controlled three-way crossover clinical effect study. Treatments consisted of six days of aural 7.5 mg TMZ or placebo gel at home, and 1.88 mg mirtazapine orally once in clinic. Owners documented appetite, rate of food ingestion, begging, activity and vocalization daily at home. On day six, food consumed, activity and vocalization were documented in hospital and trough and peak serum mirtazapine levels obtained. Serum mirtazapine and gel concentrations were measured using liquid chromatography/tandem mass spectrometry. Results Phase I: Administration of TMZ achieved measureable serum mirtazapine concentrations. AUC0-48 of multidose 7.5 mg TMZ was significantly higher than single dose 1.88 mg OMZ (P = 0.02). Phase II: Client-owned cats administered TMZ had a significant increase in appetite (P = 0.003), rate of food ingestion (P = 0.002), activity (P = 0.002), begging (P = 0.002) and vocalization (P = 0.002) at home. In hospital there was a significant increase in food ingested with both TMZ and OMZ compared to placebo (P < 0.05). Gel concentrations ranged from 87%–119% of target dose. Conclusions and relevance 7.5 mg daily TMZ achieves measureable serum concentrations and significant appetite stimulation despite variance in compounded gel concentrations, but side effects denote a lower dose is indicated.

Objectives The aim of this study was to assess the appetite stimulation properties of compounded transdermal mirtazapine (CTM) in cats with chronic kidney disease (CKD). Methods Two sequential double-blind placebo-controlled crossover prospective studies were performed in client-owned cats with stable stage 2 or 3 CKD and a history of decreased appetite. In the first study nine CKD cats were randomized to receive 3.75 mg/0.1 ml CTM gel or placebo on the inner pinna every other day for 3 weeks, then, after a 4 day washout period, the cats were crossed over to the alternate 3 week treatment. In a second study, 10 CKD cats were randomized to receive 1.88 mg/0.1 ml CTM or placebo on the same schedule. Physical examination and serum biochemistry were performed before and after each treatment period, and owners kept daily logs of appetite, activity and eating behaviors. Mirtazapine concentrations in CTM gels and steady-state mirtazapine serum concentrations were measured using liquid chromatography/tandem mass spectrometry. Results Administration of both 3.75 mg and 1.88 mg CTM resulted in a statistically significant increase in weight ( P = 0.002 for both), increase in appetite ( P = 0.01 and P = 0.005, respectively), and increase in rate of food consumption ( P = 0.03 and P = 0.008, respectively). No significant difference in activity or vocalization was seen at either dose; however, individual cats experienced excessive meowing. Median weight increase for the 3.75 mg arm was 0.22 kg (range 0.04–0.44 kg), while median weight increase for the 1.88 mg arm was 0.26 kg (range –0.25 to 0.5 kg). Improvement in body condition score was seen in 5/9 cats in the 3.75 mg arm (P = 0.04) and 6/10 cats in the 1.88 mg arm (P = 0.004). Conclusions and relevance CTM increased appetite and resulted in weight gain in CKD cats despite significant inconsistencies in compounding, and may benefit cats in countries where an approved product is not available.

Objectives The aims of this study were to determine the side effect frequency and serum and urine drug concentrations of amoxicillin–lavulanic acid in cats with and without azotemic chronic kidney disease (azCKD). Methods Owners whose cats had been prescribed amoxicillin–clavulanic acid completed a survey regarding the occurrence and type of side effects, and whether treatment was altered as a result. Cats were defined as azCKD (serum creatinine concentration >2.0 mg/dl, urine specific gravity [USG] <1.035 with a clinical diagnosis of CKD) and without azCKD (serum creatinine concentration <2.0 mg/dl). Data were assessed with Fisher’s exact test. Serum and urine samples were obtained from client-owned cats with azCKD (n = 6) and without azCKD (n = 6, serum creatinine concentration <1.8 mg/dl, USG >1.035) that were receiving amoxicillin–clavulanic acid. Amoxicillin and clavulanic acid were measured with liquid chromatography coupled to tandem mass spectrometry and compared between groups with a Mann–Whitney test. Correlation between serum creatinine and drug concentrations in urine and serum was determined using Spearman’s rank test. Results Sixty-one surveys were returned (11 azCKD cats and 50 without azCKD cats). No significant difference in the presence of side effects or type of side effects was seen between groups; however, significantly more azCKD cats had more than one side effect ( P = 0.02). More owners of azCKD cats reported that an alteration in treatment plan was necessitated by side effects (55% vs 12%; P = 0.008). Urine amoxicillin was significantly lower in cats with azCKD ( P = 0.01) and serum amoxicillin trended toward significance ( P = 0.07). Serum amoxicillin concentration was positively correlated with serum creatinine ( P = 0.02; r = 0.62) and urine amoxicillin concentration was negatively correlated with serum creatinine ( P = 0.01; r = –0.65). Conclusions and relevance The data suggest that cats with azCKD have altered pharmacokinetics of amoxicillin, which may contribute to an increased incidence of multiple side effects.

BackgroundLiver disease (LD) prolongs mirtazapine half‐life in humans, but it is unknown if this occurs in cats with LD and healthy cats.Hypothesis/ObjectivesTo determine pharmacokinetics of administered orally mirtazapine in vivo and in vitro (liver microsomes) in cats with LD and healthy cats.AnimalsEleven LD and 11 age‐matched control cats.MethodsCase‐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.ResultsThere 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 ImportanceCats with LD might require less frequent administration of mirtazapine than normal cats.

The bioavailability of lithium citrate syrup was compared with that of regular lithium carbonate tablets in 18 healthy male human volunteers. Blood samples were collected up to 48 h after dosing. Lithium serum concentrations were determined by means of AAS. The absorption rate following oral administration of the syrup was greater (tmax 0.8 h) than following administration of regular tablets (tmax 1.4 h). Maximum lithium serum concentrations, however, were only about 10 per cent higher after syrup dosing and serum concentrations resulting from syrup and tablets were almost superimposable from 2 h after dosing. The terminal half-life of lithium was found to be 22 h after syrup as well as after tablet dosing. No side-effects were observed during the study. The bioavailability of lithium from syrup relative to tablets was found to be bioequivalent with respect to the maximum lithium serum concentration and the extent of drug absorption (AUC).