摘要:

Summary—Use of the Hill equation in plotting the results of toxicological experiments offers the following advantages:1In dose/effect relationships, the maximum response RMcan be accurately determined by means of a described new noniterative algebraic method, from both hyperbolic and sigmoidal responses expressed in natural (nontransformed) units. The Hill coefficient (n) and the dose giving 50% (f50) or X% (fx) of RM, as well as their SD, are accurately deduced.2In time‐course experiments with sigmoidal shape, an additional set of parameters, readily available from the former basic 3, makes it possible to avoid arbitrary choices, such as the time at which a percentage or mortality is considered. The slopes of the tangents at the inflexion point (maximum rate of response) and at half‐maximum effect, then the coordinates of these points and the horizontal intercept of the tangent at inflexion point (as an index of initial lag‐phase) will give increasing and decreasing functions of doses, respectively, depending on RM, f50, and (n).3The processes described first allow the classical parameters LD50(or LDx) and LT50(or LTx: X%‐lethality time) to be calculated with high algebraic accuracy, in addition to RMand (n), both of which are of great interest in the general case of ligand‐receptor interactions. Thus, the deduced set of additional indexes, not readily available from classical “Probits‐type” transformations, eliminates the mortgage of subj

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00024.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—The kinetics of ethyl loflazepate were studied in patients with various degrees of renal failure. A strong correlation was noted between urinary excretion of metabolite loflazepate and creatinine clearance. In contrast, elimination half‐life and total plasma clearance of the sum of loflazepate+descarboxyloflazepate seemed to be independent of the degree of renal impairment. These results indicate the absence of a risk of accumulation of the 2 main and active metabolites of ethyl loflazepate in patients with renal fail

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00025.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—The pharmacokinetics of the tricyclic antidepressant amineptine (Survector®) and its main metabolite were studied in 12 young healthy adults (6 men, 6 women; mean age 35.8 yr). Plasma samples were taken over 24 h following a single oral dose of 100 mg amineptine chloryhdrate. Plasma levels of both compounds were determined by means of high performance liquid chromatography.Amineptine was rapidly absorbed. Mean peak plasma concentrations of amineptine and its metabolite occurred 1 h and 1.5 h, respectively, after product administration. The mean apparent volume of distribution was large: 2.4 l.kg−1. Elimination was rapid; the mean half‐lives of the 2 compounds were short: 0.8 h for amineptine and 2.5 h for the metabolite. The mean apparent plasma clearance of amineptine was high (124.8 l.h−1).When the results were adjusted for body weight and surface area, no significant difference in pharmacokinetic parameters was found between men and women.Given its pharmacokinetic characteristics there is no risk of amineptine accumulation and thus it is a particularly easy drug to manage.A standard dosage of amineptine was defined for use in healthy youn

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00026.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—The pharmacokinetics of the narcotic analgesic dextromoramide was investigated by means of a specific GC‐MS method in 9 patients who were given a single oral dose of the drug (7.5 mg) together with an anticholinergic before undergoing minor orthopedic surgery. Dextromoramide was rapidly absorbed from the gastrointestinal tract, with peak plasma levels between 68 and 177 μ/L usually achieved within 0.5‐4.0 h after dosing. In 5 patients, the decline of plasma concentrations after the peak followed a biphasic pattern, with half‐lives of 0.4‐1.6 h for the first phase and 6.3–21.8 h for the terminal phase. In the remaining patients, no clear‐cut biphasic pattern was seen and half‐lives calculated over the period between 4 h and 10 h after administration ranged from 1.5 to 4.7 h. Apparent clearance and volume of distribution values ranged from 0.06 to 0.36 l.h−1.kg−1and from 0.6 to 2.4 l.kg−1, respectively. Less than 0.06% of the dose was excreted unchanged in urine within 8 h of administration. The concentration of the drug in a CSF sample collected 1 h after dosing was below the limit of detection (

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00027.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—[3H]52770 RP, a PAF antagonist, was found to bind with high affinity and in a reversible manner on specific and saturable binding sites in guinea pig cortical membranes. Scatchard analysis revealed the presence of one class of binding sites with an equilibrium dissociation constant of 0.38 nM and a Bmaxof 1190 fmol/mg protein. However, these binding sites did not correspond to the PAF receptors described with this ligand in platelet plasma membranes; indeed, PAF and its analogs were unable to displace [3H]52770 RP binding in guinea pig brain. Therefore, one may conclude that [3H]52770 RP in guinea pig brain labels acceptor or recognition sites, rather than true receptor site

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00028.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—We investigated the pressor response to oral tyramine before and during treatment with moclobemide, a selective monoamine oxidase‐A inhibitor, in 10 depressed patients. Before moclobemide therapy, tyramine was associated with a mean (SD) maximum rise in systolic blood pressure of 4.0 (5.2) mmHg, whereas during moclobemide treatment, tyramine was associated with an increase of 24.9 (14.2) mmHg. Only one subject failed to demonstrate an increased pressor response while taking moclobemide. Moclomebide potentiates the pressor response to oral tyramine, but is safer than older nonselective monoamine oxidase inhibit

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00029.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—Bopindolol was given to hypertensive patients in a single daily dose ranging from 1 to 4 mg. In 86.7% of the patients diastolic blood pressure was reduced by 10 mmHg or more, or lowered to below 90 mmHg, already during the first 4 wk of treatment. Inulin clearance decreased by 10%; PAH and creatinine clearance, blood urea nitrogen, and serum creatinine were unchange

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00030.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—Nifedipine (10 mgtid) or placebo was administered in a randomized double‐blind trial for 1 wk to 2 groups of 10 mildly hypertensive euthyroid patients. Hormonal concentrations (thyrotropin [TSH], prolactin [PRL], thyroxin, triiodothyronine, and reverse triiodothyronine) before and during a TRH test were assessed in the 2 groups before (D0) and after (D7) each treatment. Parameters of the TRH test were determined (peak values, area under the curve [AUC], release [Kr], and elimination [Ke] rate constants) and their D7:D0 ratios were compared in the 2 groups. The TSH (peak values and Kr) and PRL (peak values and AUC) responses to TRH were significantly decreased in the nifedipine group compared to the placebo group. Neither basal nor TRH‐stimulated thyroid hormone levels were modified. These results confirm experimental data but seem to be clinically irrel

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00031.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Summary—Hemodynamic effects of LND‐623, a new aminosteroid lacking the C17 lactone ring and the C14 hydroxyl group common to the natural glycosides, were studied in the pentobarbital‐anesthetized dog and compared to those of its 20α‐isomer LND‐369 and of digoxin and digoxigenin‐rhamnoside (DRh). Twenty‐four mongrel dogs were divided into 4 groups. Group I received either LND‐623 or saline on study day 1 and the other drug or saline 1 wk later. Saline was replaced by digoxin in group II, digoxigenin‐rhamnoside in group III, and LND‐369 in group IV. All drugs except LND‐369 were infused as 3.10−1mol.kg−1.min−1over 20 minutes. LND‐369 was infused at twice the dose.LND‐623 increased left ventricular dP/dt for at least 3 h with a peak at end‐infusion or 15 min later, accompanied by a transient vasopressor effect. LND‐369 induced, at twice the dose, an inotropic effect of comparable magnitude but of shorter duration. Inversely, it provoked a more marked and prolonged vasopressor effect than its 20β‐isomer, LND‐623. Maximal digoxin inotropic effect occurred later but was of comparable magnitude to that induced by LND‐623. Its vasopressor effects reached a plateau rapidly and remained sustained until min 200. Digoxigenin‐rhamnoside inotropic but not vasopressor effects are weaker than those of LND‐623.It is concluded that LND‐623, although lacking the most common structural features of the natural cardiac glycosides, provoked rapid and sustained inotropic activities with transient vasopressor effects. These time‐course effects differ from digoxin, and these differences are unrelated to their sugar‐moiety characteristics. LND‐62

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1989.tb00032.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY