The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

Biological activity of fluorinated 3,4-dihydroisoquinolines

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 26, No. 1, pp. 44–45, January, 1992.     

Carotid-cavernous sinus fistula associated with a primitive trigeminal artery

Carotid-cavernous sinus fistulas are not rare, but they have never been reported in association with persistent primitive trigeminal artery. We recently encountered such a case. The Jaeger-Hamby procedure was employed, with mandatory occlusion of the primitive trigeminal artery.     

Model parameters of the smooth pursuit eye movement system with electrooculogram

The visual pursuit test is a method that collects and analyzes the characteristics of pursuit eye movements and examines the function of the eye movement system. This paper analyzes the model parameters of the smooth pursuit eye movement system in order to explore a method for improving the analysis. The input-output relationship of the smooth pursuit system can be expressed by a quasilinear model. We compute the model parameters (gain, phase, spectral purity, cross covariance) by digital signal processing. Eye movement is recorded by electrooculogram. Both eyes are tested individually. The visual target moves at frequencies of 0.2, 0.4, 0.8, 1.2, and 1.6 Hz. Ranges are gain, 1.01 to 0.70; phase, -0.1 ° to -66 °; spectral purity, 0.97 to 0.70; and cross covariance, 0.99 to 0.26. We tested 40 normal subjects as well as patients with ataxia (8), vertigo (18), and ophthalmoplegia (9). The oculomotor system of normal subjects functions as a linear system in the performance of this test at 0.2 to 0.8 Hz. The spectral purity dropped to about 0.70 at 1.6 Hz. The variability of all measures increases greatly at 1.6 Hz, which indicates that this target motion exceeds the tracking ability of many normal subjects and that the oculomotor system of normal subjects functions as a nonlinear system in this condition. Statistical tests show no significant differences between sex, age, and the two eyes. The model parameters tentatively proved effective in clinical application.     

脊髓手术中体感诱发电位监测的临床研究

报告３０例脊髓手术中体感诱发电位（ＳＥＰ）连续监测的临床研究结果。ＳＥＰ记录包括脊髓ＳＥＰ（ＳＳＥＰ）和皮层ＳＥＰ（ＳＣＥＰ）。麻醉药物对ＳＥＰ有一定程度影响，ＳＣＥＰ相对较大。认为，至少术中ＳＥＰ潜伏期延长不超过８％和波幅降低不超过５０％，不会引起术后并发症，超过该范围由于病例较少，尚不能肯定与预后的关系，需进一步探讨。     

Studies on the properties of some peripheral MAO inhibitors

1. Studies were carried out on three monoamine oxidase (MAO) inhibitors, two of which, debrisoquine and para- hydroxyphenelzine, are purported to be peripheral inhibitors and one, phenelzine, is a peripherally acting inhibitor, which has been included for comparitive purposes. 2. All three showed varying degrees of specificity towards MAO type A. 3. The action of debrisoquine was very rapid as was that of para- hydroxyphenelzine. 4. The inhibition caused by debrisoquine was competitive and reversible, while that caused by both phenelzine and para- hydroxyphenelzine was irreversible. 5. The inhibition caused by debrisoquine appeared to be unaffected by the pH of the medium.