Single-dose pharmacokinetics and cardiovascular effects of oral pimobendan in healthy cats.

INTRODUCTION: To investigate the pharmacokinetics and pharmacodynamics of oral pimobendan in conscious, healthy cats. ANIMALS: Eight healthy adult cats. MATERIALS AND METHODS: A randomised, single-blinded, crossover design was used. Two oral doses of pimobendan (0.625-mg [LD], 1.25-mg [HD]) and a control substance (3-mL water) were administered to each cat. Blood collection, echocardiography, and oscillometric blood pressure measurements were performed repeatedly for 12 h following each dose. Plasma concentrations of pimobendan and the active metabolite, O-desmethylpimobendan (ODMP), were quantified using ultra-high-performance liquid chromatography tandem mass spectrometry. Cardiovascular parameters were evaluated for between- and within-treatment effects over time using linear mixed modelling. RESULTS: Pimobendan was rapidly absorbed and converted to ODMP with the pimobendan AUC0-∞ greater than ODMP AUC0-∞ (ODMP:pimobendan AUC0-∞ ratio 0.6 [LD] and 0.5 [HD]) despite a longer elimination half-life of ODMP (pimobendan t1/2 0.8 h vs. ODMP t1/2 1.6 h [LD]; pimobendan t1/2 0.7 h vs. ODMP t1/2 1.3 h [HD]). Averaged across all time points, pimobendan increased several measures of systolic function; however, its effect could not be further characterised. Although treatment was well-tolerated, two cats vomited following HD and another had a ventricular premature beat recorded following LD. CONCLUSIONS: The lower ODMP:pimobendan AUC0-∞ ratio compared to that observed previously in dogs suggests reduced metabolism in cats. Treatment effects were observed in measures of systolic function; however, the duration of action and differences in effects between the two pimobendan doses could not be characterised. Further studies are required to evaluate pimobendan in feline cardiovascular medicine.

Comparison of the multidetector-row computed tomography findings of IgG4-related sclerosing cholangitis and extrahepatic cholangiocarcinoma.

AIM: To compare the multidetector-row computed tomography (MDCT) findings of IgG4-related sclerosing cholangitis (IgG4-SC) and extrahepatic cholangiocarcinoma (EH-CCA). MATERIALS AND METHODS: Two radiologists who had no knowledge of the patients' clinical information retrospectively evaluated the CT findings of patients with IgG4-SC (n=33) and EH-CCA (n=39) on a consensus basis. Another radiologist measured the biliary lesions. IgG4-SC was diagnosed using the Japan Biliary Association criteria (2012) or the Mayo Clinic's HISORt criteria. EH-CCA was diagnosed based on surgical findings. RESULTS: Compared with EH-CCA, IgG4-SC exhibited the following findings significantly more frequently: (a) wall thickening alone, (b) concentric wall thickening, (c) smooth inner margins, (d) homogeneous attenuation in the arterial phase, (e) a lesion involving the intrapancreatic bile duct, (f) smooth outer margins, (g) fully visible lumen, (h) a funnel-shaped proximal bile duct, (i) skip lesions, and (j) abnormal pancreatic findings. Conversely, (k) dual-layered attenuation in all phases was significantly more common in EH-CCA. The specificity values of parameters (e-k) were >80%. Regarding dimensions, (l) the biliary lesions were longer in IgG4-SC than in EH-CCA. (m) The diameters of the dilated proximal common bile duct and (n) the dilated proximal intrahepatic bile duct were smaller in IgG4-SC than in EH-CCA. CONCLUSION: A number of CT findings are useful for differentiating between IgG4-SC and EH-CCA. CT findings (e-k) are particularly useful for this purpose.

Pharmacokinetics and cardiovascular effects following a single oral administration of a nonaqueous pimobendan solution in healthy dogs.

Pimobendan is an inodilator used in the treatment of canine congestive heart failure (CHF). The aim of this study was to investigate the pharmacokinetics and cardiovascular effects of a nonaqueous oral solution of pimobendan using a single-dose, operator-blinded, parallel-dose study design. Eight healthy dogs were divided into two treatment groups consisting of water (negative control) and pimobendan solution. Plasma samples and noninvasive measures of cardiovascular function were obtained over a 24-h period following dosing. Pimobendan and its active metabolite were quantified using an ultra-high-performance liquid chromatography-mass spectrometer (UHPLC-MS) assay. The oral pimobendan solution was rapidly absorbed [time taken to reach maximum concentration (Tmax ) 1.1 h] and readily converted to the active metabolite (metabolite Tmax 1.3 h). The elimination half-life was short for both pimobendan and its active metabolite (0.9 and 1.6 h, respectively). Maximal cardiovascular effects occurred at 2-4 h after a single oral dose, with measurable effects occurring primarily in echocardiographic indices of systolic function. Significant effects persisted for <8 h. The pimobendan nonaqueous oral solution was well tolerated by study dogs.

[Episode secretion of LH releasing hormone and LH in peripheral plasma of women with and without ovulatory disturbances].

We studied the secretory dynamics of plasma luteinizing hormone releasing hormone (LHRH) and luteinizing hormone (LH) in 5 normal ovulatory women during the early follicular phase, and 29 cases of ovuluatory disturbances using radioimmunoassay methods. All of the normal ovulatory women demonstrated one or two pulsatile LHRH releases in 3 or 4 hours. The height of LHRH secretory spikes was observed to be between 1.4 and 9.2 pg/ml. Plasma LH episodic secretion was related to LHRH episodic secretion. In 15 out of 27 cases of of ovulatory disturbances except cases with primary ovarian dysfunction, the LH episodic secretion revealed a significant decrease in pulse frequency. In 13 out of 16 cases of ovulatory disturbances, the height of LHRH secretory spikes was not greater than 1.3 pg/ml. This study indicates that the main causes of ovulatory disturbances are decrease in LHRH and LH episodic secretion. In all cases treated with clomphene, the plasma LHRH pulse increased after treatment. But in the cases where ovulation was not induced by clomiphene citrate, the plasma LH pulse did not increase as the LHRH pulse increased.