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R J Herman

Publications and source records attributed to R J Herman.

26 records · Page 2Linked to original sources
PubMed1988

Effect of dose on the glucuronidation and sulphation kinetics of diflunisal in man: single dose studies.

1. The effect of dose (100 mg, 250 mg, 500 mg, 750 mg and 1000 mg) on the glucuronidation and sulphation of diflunisal was studied in six healthy volunteers. 2. Total urinary recovery ranged from 78.9 +/- 11.9% to 91.5 +/- 18.7% of the administered dose. Urinary recovery (normalized for total urinary recovery) of diflunisal sulphate (DS) significantly increased with dose from 9.3 +/- 3.7% to 18.1 +/- 4.8%. 3. Normalized urinary recovery for diflunisal phenolic glucuronide (DPG) was unaffected by dose (range: 30.6 +/- 3.8% to 40.6 +/- 6.6%). Normalized urinary recovery for the acyl glucuronide (DAG) significantly decreased from 52.3 +/- 4.6% to 40.2 +/- 3.4% as the dose increased. 4. Total plasma clearance of diflunisal significantly decreased from 14.4 +/- 1.4 ml min-1 to 8.7 +/- 1.4 ml min-1 as the dose increased from 100 mg to 750 mg. A further increase in dose to 1000 mg resulted in an unexplained increase in total plasma clearance to 10.3 +/- 1.8 ml min-1. 5. Dose-dependent plasma clearance of diflunisal was caused mainly by saturation of the formation of DAG, whereas the formation of DS and DPG were relatively unaffected by dose.

Adolescent↗
PubMed1985

Effects of age on meperidine disposition.

Elderly patients appear to be more sensitive to meperidine than younger ones; however, the contributions of altered dynamic and kinetic factors are not clear. Accordingly, seven healthy normal men aged 60 to 79 yr were simultaneously given 25 mg meperidine HCl intravenously and the same dose of deuterium-labeled drug either orally or intramuscularly (deltoid). Blood and urine samples collected over 24 hr were analyzed by gas chromatography-mass spectrometry and kinetic data were compared to those previously obtained in a young cohort. Systemic clearance (8.61 +/- 2.22 ml/min/kg), apparent oral clearance (17.5 +/- 5.5 ml/min/kg), terminal t1/2 (6.98 +/- 1.86 hr), and the blood/plasma concentration ratio (0.97 +/- 0.12) in the elderly did not differ from those in younger subjects. In the elderly, however, the initial (2.4 +/- 0.8 l/kg) and the steady-state (4.6 +/- 0.9 l/kg) volumes of distribution were 300% and 135% values in the young. No age differences were found in absorption profiles or bioavailability after oral (F = 0.49 +/- 0.08) or intramuscular (F = 0.94 +/- 0.04) dosing. It appears that age-related alterations in drug disposition per se do not account for changes in clinical efficacy of meperidine in the elderly.

Administration, Oral↗
PubMed1984

Enzyme induction and beta-adrenergic receptor blocking drugs.

All beta-adrenergic receptor blockers that require metabolism prior to elimination are potentially subject to drug interactions due to enzyme induction. However, data is only available in man for propranolol, metoprolol and alprenolol. Cross-sectional population studies suggest that environmental factors, such as smoking in the young, are able to influence the oral clearance of propranolol. Long-term studies comparing within-subject clearances of metoprolol, alprenolol and propranolol before and after rifampicin and pentobarbitone, indicate that oral clearance is increased by 50%-500%. Inducing agents can influence intrinsic clearance, liver blood flow, and protein binding in addition to drug metabolising ability, indicating that changes in pharmacokinetic disposition may be complex. Enzyme induction exhibits both dose and time dependency relationships. The maximal extent of enzyme induction is similar between subjects. The range of intersubject variation in drug metabolism is similar before and after induction. The reduction in steady-state beta-adrenergic receptor drug concentration following enzyme induction is sufficiently large that an altered pharmacodynamic response would be expected if no dosage modification is made.

Adolescent↗
PubMed1983

Induction of propranolol metabolism by rifampicin.

The effect of rifampicin on the blood concentration-time curve of propranolol at steady-state following oral administration of 120 mg every 8 h was investigated in six normal, young, male subjects. After an initial 2 week dosing period, all individuals additionally received 600 mg rifampicin daily for 3 weeks followed by a 4 week period during which again only the propranolol was given. In four of the subjects the effects of 900 and 1200 mg rifampicin daily was also studied. Changes in disposition were assessed by estimation of propranolol's oral clearance and elimination half-life during the dosage interval. Rifampicin (600 mg/day) caused a large increase in propranolol's oral clearance (35.7 +/- 16.3 vs 96.1 +/- 26.9 ml min-1 kg-1, mean +/- s.d.), but neither the elimination half-life nor extent of plasma binding were affected. Increasing the daily dosage to 900 and 1200 mg did not cause any additional changes in oral clearance. Four weeks after discontinuing rifampicin, propranolol's oral clearance had essentially returned to its pre-induction level. The oral clearance of propranolol was significantly smaller (89.5 +/- 14.4%) during the dosage interval immediately after administration of the last rifampicin dose than the value measured 24 h later. The findings are consistent with rifampicin causing induction of the drug metabolizing enzymes responsible for propranolol's biotransformation. The marked reduction in the steady-state propranolol blood concentration that results from chronic rifampicin administration would be expected to result in a significant change in clinical effectiveness of the beta-adrenoceptor blocker when the two drugs are used concurrently.

Adult↗
PubMed1981

Hemodynamic assessment of transluminal angioplasty for lower extremity ischemia.

The results of percutaneous transluminal angioplasty (PTA) for 56 ischemic lower extremities in 51 patients were analyzed. Indications for balloon catheter dilatation were intermittent claudication in 46 limbs (82.1%), rest pain in five (8.9%), and ischemic ulceration in five (8.9%). Balloon dialation was technically successful in 16 of 17 iliac segment lesions (94.1%) with symptomatic improvement in each instance. Nine of the 16 limbs were hemodynamically improved with a significant increase (less than 0.15) in ankle systolic pressure index. Four additional limbs had improvement in the thigh index. The remaining three limbs were hemodynamically unimproved. During average follow-up of 7.1 months, the 13 initially improved limbs remained hemodynamically improved. Thirty-one of 42 femoropopliteal dilatations (73.8%) were technically successful, with uniform symptomatic improvement. Of these 31 limbs, 26 had a significant initial increase in ankle index, one had improvement in distal thigh index only, and the remaining four limbs were hemodynamically unimproved. During mean follow-up of 8.4 months in the 27 limbs that initially were improved after femoropopliteal dilation, the pressure index returned to the pre-PTA level in 12 instances (44.4%). These results indicate that PTA is useful in selected short-segment iliac lesions. Balloon dilation of femoropopliteal lesions was less successful and its application requires further evaluation. This study demonstrates the need for close monitoring of the objective hemodynamic response, as well as symptomatic and angiographic results, in establishing the proper role of PTA in the treatment of lower extremity ischemia.

Adult↗
PubMed1980

Computed tomography in the diagnosis of aortic aneurysm dissection or traumatic injury.

Thirty patients thought to have an atherosclerotic thoracic aneurysm or chronic aortic dissection were evaluated by computed tomography (CT) and the findings compared with those from conventional radiography, thoracic aortography, and surgery. In all cases, CT defined the lesion and correlated well with angiography. Staging of atherosclerotic aneurysms was possible, and CT also demonstrated the relationship between true and false lumina in aortic dissections; however, aortography was often necessary to differentiate a dissection from an aneurysm or for staging. The relative value of CT and aortography is discussed.

Adult↗
PubMed1980

Descending venography: a method of evaluating lower extremity venous valvular function.

Recently developed surgical techniques for the correction of lower extremity venous insufficiency have renewed interest in venous valvular functions. To assess the value of descending venography in the evaluation of venous valvular incompetence, this technique was compared with bidirectional Doppler ultrasound and ascending venography in the examination of 32 patients with clinical signs of chronic venous insufficiency. Twelve of these patients underwent surgery to valvular incompetence, and all underwent descending venography and Doppler ultrasound examinations postoperatively. Descending venography proved to be an effective, accurate method of diagnosing venous valvular incompetence of the saphenofemoral system.

Adult↗