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Biomedical subjects

J L Schelling

Publications and source records attributed to J L Schelling.

At least 37 records · Page 2Linked to original sources
PubMed1982

Enalapril maleate and a lysine analogue (MK-521): disposition in man.

1 The disposition of two angiotensin converting-enzyme inhibitor drugs was studied in normal volunteers. One drug was enalapril maleate (MK-421), which requires in vivo esterolysis to yield active inhibitor (MK-422). The other was a lysine analogue of MK-422 (MK-521), which requires no bioactivation. 2 Absorption of enalapril maleate (10 mg, p.o.) was rapid, with peak serum concentrations of enalapril observed 0.5-1.5 h after administration. Based upon urinary recovery of total drug (enalapril plus MK-422), absorption was at least 61%. Bioactivation appeared to be largely post-absorptive. From the ratio of MK-422 to total drug in urine, the minimum extent of bioactivation was estimated at 0.7. 3 A similar dose of MK-521 was absorbed more slowly, reaching peak serum concentrations 6-8 h following drug administration. Minimum absorption, based upon urinary recovery, was 29%. 4 Serum concentration v time profiles for both drugs were polyphasic and exhibited prolonged terminal phases. 5 Recovery in urine and faeces of administered enalapril maleate (intact and as MK-422) was 94%. Recovery of MK-521 was 97%. These results indicate lack of significant metabolism of these agents, apart from the bioactivation of enalapril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

Enalapril maleate and a lysine analogue (MK-521) in normal volunteers; relationship between plasma drug levels and the renin angiotensin system.

1 Two single doses of 10 mg each of the converting enzyme inhibitor enalapril maleate or MK-421 and of its lysine analogue (MK-521) were administered p.o. to twelve male volunteers. 2 The active diacid metabolite of MK-421 and the lysine analogue were determined by radioimmunoassay and MK-421 by the active metabolite method following in vitro hydrolysis. 3 Peak serum levels of MK-421, active metabolite and lysine analogue were reached within 1, 3 to 4, and 6 h respectively. Practically all MK-421 had disappeared from serum within 4 h. 4 A close correlation between percent inhibition of plasma converting enzyme activity and the serum concentration of active metabolite was observed ( r = 0.98, n = 171, P less than 0.001). Similarly, converting enzyme blockade as expressed by the ratio plasma angiotensin II/angiotensin I was closely correlated with serum active metabolite levels (r = 0.93, n = 15, P less than 0.001).

Adult↗
PubMed1981

Effect of a new angiotensin converting enzyme inhibitor MK 421 and its lysine analogue on the components of the renin system in healthy subjects.

1 MK 421 and its lysine analogue are two new inhibitors of angiotensin converting enzyme. Ten mg of both compounds were each given p.o. to 12 normotensive volunteers to determine their effect on the various components of the renin angiotensin aldosterone system. 2 Plasma converting enzyme activity decreased to very low levels within 3 to 4 h to recover only slowly over the next 72 h. Plasma angiotensin II and aldosterone also fell but returned to baseline within 24 h, whereas plasma renin activity rose reflecting the low angiotensin II levels. 3 There was a close correlation between both angiotensin II and aldosterone levels and the logarithm of plasma converting enzyme activity demonstrating that angiotensin II and aldosterone fell only when converting enzyme activity was reduced to very low levels. 4 Mean hourly urinary sodium excretion increased markedly 6 to 10 h post-drug, while blood pressure decreased slightly. Both drugs were well tolerated. 5 Thus 10 mg of MK 421 or its lysine analogue given orally are effective and long acting angiotensin converting enzyme inhibitors.

Adult↗
PubMed1981

Immersion and venous occlusion plethysmography in patients with idiopathic orthostatic hypotension.

In 3 patients suffering from idiopathic orthostatic hypotension (Shy-Drager's syndrome) venous distensibility was measured by occlusion plethysmography in supine and upright position. In this latter position, venoconstriction was absent, contrasting with the marked venoconstriction observed in normal volunteers studied under identical conditions. Venous occlusion plethysmography therefore seems to be useful to detect the autonomic defect leading to venous pooling. These patients were also immersed in water to the mid-abdomen while standing. This maneuver fully abolished orthostatic hypotension. Immersion is useful in motivating these patients to accept treatment by counterpressure garments, and makes early active physiotherapy possible.

Aged↗
PubMed1979

Judgments of trained observers on adverse drug reactions.

Patients (672) admitted to a department of medicine during five consecutive months were followed by an investigator who identified 110 clinical manifestations which could have been considered adverse drug reactions. From these, 42 were excluded because they did not correspond to the definition of adverse reaction or they were inadequately documented. The remaining 68 cases were submitted to three independent observers who had to reply to a series of questions; from these replies five degrees of probability for the reaction itself were deduced. Reactions (54; 49% of the manifestations reported) were considered as certain or probable by at least two observers, but only 27 rections of these (25%) were attributed to the same drug by all three observers. There was a low level of agreement between any two observers (paired agreement ratio: 0.6 to 0.7) and little difference of agreement between any one observer and each of the others (personal agreement ratio: 0.6 to 0.7).

Drug-Related Side Effects and Adverse Reactions↗
PubMed1978

[Frequency of drug prescriptions and their adverse effects in a medical department].

The enquiries carried out in our unit since 1971, in some 1600 patients who received in all more than 13000 drug prescriptions and who were observed during 3 periods whose total duration was 12 months, prompt the following conclusions. The number of adverse reactions in which the relationship of cause and effect with one or several drugs was either definite or probable amounted to 217, 2--3% among patients at admission and 5--11% of patients during their hospital stay. The average number of prescriptions per patient remained stable and the average number of drug reactions per 100 prescriptions varied from 0.6 to 1.6. Severe drug reactions occurred in 1.1% of patients at admission and 1.1% of patients during their hospital stay.

Drug Prescriptions↗
PubMed1978

[Serum and joint levels of cefacetrile during its administration for septic arthritis].

Six patients, five of whom had normal and one impaired renal function, and all suffering from purulent arthritis caused by cephalosporin-sensitive germs, were given a seven-day course of 8 g cephacetrile daily. On the first day, 6 g were administered by continuous intravenous infusion at the rate of 500 mg/h, followed by 2 g over a further 45 min. On days 2 to 7, the patients received 2 short infusions of 4 g each at an interval of 12 h. In four patients with normal renal function, serum half-life ranged from 0.8 to 1.4 h, serum levels during continuous infusion from 19 to 31 microgram/ml, and total clearances from 265 to 434 ml/min. In one patients, these values were 1.6 h, 70 microgram/ml and 131 ml/min respectively (small volume of distribution). The concentrations in the synovial fluid varied from 2 to 29 mcirogram/ml; they were generally lower than the serum levels, but clearly exceeded the minimum inhibitory concentrations for germs commonly present in purulent arthritis. In five patients, the synovial fluid became germ-free and the arthritis was clinically cured. In the case presenting with renal insufficiency, the serum half-life was 5.8 h. During continuous administration, a steady state was not attained; peak serum levels amo9nted to 75 microgram/ml and the total clearance to 61 ml/min. The cephacetrile concentrations in the synovial fluid were very high (26 and 67 microgram/ml). In this case, in which the renal insufficiency associated with mycosis fungoides was present before the treatment, renal function deteriorated futher during treatment while the arthritis improved.

Adolescent↗
PubMed1978

Effect of the menstrual cycle, oral contraception and pregnancy on forearm blood flow, venous distensibility and clotting factors.

Forearm blood flow, venous distensibility and various clotting factors were determined in 118 apparently healthy women (mean age 26 years), either during the menstrual cycle, or while taking a combined contraceptive (A) with high progestin:estrogen ratio (d-norgestrel 0.125 mg + ethinylestradiol 0.03 mg), or a sequential contraceptive (B) with low progestin: estrogen ratio (megestrol 0.1/1 mg + ethinylestradiol 0.1 mg), or in the 1st, 2nd and 3rd trimester of pregnancy. Venous distensibility in women taking contraceptive A was higher than in other women during the follicular phase of a normal menstrual cycle. Venous distensibility was not affected by contraceptive B. Blood flow and blood pressure remained unchanged by contraceptives A and B. Fibrinogen concentration was increased by both contraceptives, factor VII was either decreased (A) or unchanged (B), and factor X was either unchanged (A) or increased (B). The oral contraceptive with the high progestagen component appeared to increase venous capacitance and may induce venous stasis, whereas coagulability was particularly enhanced by the estrogen-type contraceptive. Pregnant women differed from women on oral contraceptives in regard to peripheral circulation; they showed a tremendous increase of blood flow with secondary vasodilation.

Adult↗
PubMed1977

[Consequeces of the elimination of a combination drug. Transition from combination antisacer: attention].

Antisacer compositum, a commonly prescribed speciality which associated phenobarbitone and phenytoin in a dose ratio of 1:4, was withdrawn after demonstration of a negative interaction of this formula. A retrospective analysis is presented of phenytoin plasma levels during bitherapy and after passage to monotherapy, in 13 adult epileptics followed as outpatients. Phenytoin plasma levels increased over twofold in 12 cases, of whom 5 continued to take the same doses, while 7 received higher doses on, and in one case two weeks after, the withdrawal of phenobarbitone. Plasma level decreased slightly in the thirteenth in spite of increased doses. Five phenytoin intoxications occurred after this change of prescription: one amongst the 5 cases with identical doses, and 4 amongst the 7 cases with increased doses. The initially high levels of phenytoin tend to decrease after several months. Physicians required to change the prescription should be aware of the risk of initial intoxication and later underdosage.

Adult↗
PubMed1977

[Effect of glycerol on cerebral infarct].

Intravenous administration of glycerol under double-blind conditions (25 g twice daily for 6 days) to 26 patients with cerebral infarction localized in the territory of the middle cerebral artery temporarily improved the clinical evolution, as assessed by a scoring system, in comparison with 25 patients receiving placebo infusions.

Aged↗