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1.
Am J Phys Med Rehabil ; 80(7): 494-502, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11421517

ABSTRACT

OBJECTIVE: To compare the effectiveness of an intensive group physical therapy program with individual biofeedback training for female patients with urinary stress incontinence. DESIGN: Randomized study of two therapeutic interventions consisting of a specific physical therapy program (PT) or biofeedback training (BF) daily for 4 wk, followed by a 2-mo, unsupervised home exercise program in both groups in an outpatient clinic of a large university hospital. Forty women, referred by gynecologists for nonoperative treatment of genuine stress incontinence of mild-to-moderate severity, were included. Measurements of daytime/nocturnal urinary frequency and subjective improvement of incontinence were the main outcome measures at initial presentation, after completion of the therapy program, and at follow-up after 3 mo. Standardized examinations of digital contraction strength, speculum tests, and manometric measurements were documented as secondary outcome measures. RESULTS: In the PT group, the daytime urination frequency decreased 22% after 4 wk of therapy and 19% after 3 mo (P < 0.05) from baseline. The nocturnal urination frequency was reduced by 66% after 4 wk of therapy and 62% after 3 mo (P < 0.001). In the BF group, the daily urination frequency decreased 10% after 4 wk of therapy and 5% after 3 mo (P > 0.05). The nocturnal urination frequency declined 36% after 4 wk of therapy and 66% after 3 months (P < 0.05). Subjective assessment after 3 mo showed that in the PT group, 28% of patients were free of incontinence episodes, 68% reported improved symptoms (incontinence episodes improved by >50%), and 4% were unchanged. In the BF group, 62% were free of incontinence episodes, and 38% were improved. Results of the digital contraction strength assessments, speculum tests, and manometric measurements showed statistically significant improvement in all variables in both groups after 3 months. CONCLUSION: Four weeks of both intensive group physical therapy or individual biofeedback training followed by an unsupervised home exercise program for 2 mo are effective therapies for female urinary stress incontinence and result in a significantly reduced nocturnal urinary frequency and improved subjective outcome. Only group physical therapy resulted in reduced daytime urinary frequency. BF therapy resulted in a better subjective outcome and higher contraction pressures of the pelvic floor muscles.


Subject(s)
Biofeedback, Psychology/methods , Exercise Therapy/methods , Pelvic Floor , Urinary Incontinence, Stress/rehabilitation , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Home Care Services , Humans , Manometry , Middle Aged , Muscle Contraction , Patient Education as Topic/methods , Psychotherapy, Group/methods , Referral and Consultation , Severity of Illness Index , Treatment Outcome , Urinary Incontinence, Stress/classification , Urinary Incontinence, Stress/diagnosis , Urinary Incontinence, Stress/physiopathology , Urodynamics
2.
Versicherungsmedizin ; 52(2): 81-6, 2000 Jun 01.
Article in German | MEDLINE | ID: mdl-10853376

ABSTRACT

The application of physical therapy for the treatment of chronic and recurrent pain, above all in the locomotor system, is indeed common, but its importance for pain therapy is often underestimated. The use of physical measures frequently does not follow scientific aspects. Their application without a concept and without regard to the functional and structural alteration as typical of pain in skin, connective tissue and muscles is to be criticized. A survey of the essential physical measures and their therapeutic effects is given and the principles of prescription are discussed.


Subject(s)
Pain/rehabilitation , Physical Therapy Modalities , Chronic Disease , Humans , Pain/etiology , Physical Therapy Modalities/instrumentation , Prognosis , Treatment Outcome
3.
Prev Med ; 30(2): 95-102, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10656837

ABSTRACT

BACKGROUND: Sympathetic hyperactivity is one factor for alterations encountered in the plurimetabolic syndrome, a cluster of metabolic abnormalities including obesity, hyperlipidemia, sometimes hyperglycaemia, and hypertonia. It was interesting to know if prolonged severe underfeeding (230 kcal/day) leads to decreases in catecholamines in those patients. METHODS: The plasma concentrations of catecholamines in patients (n = 16) suffering from plurimetabolic syndrome were studied before and during a 16-day period of medically controlled severe underfeeding (230 kcal/day) at rest and in response to exercise. RESULTS: During the period of underfeeding, mean norepinephrine concentrations decreased at rest from 1.45 to 0. 96 nmol/liter, and in response to exercise, from 6.1 to 3.2 nmol/liter. Epinephrine concentrations decreased from 0.15 to 0.1 nmol/liter and from 0.26 to 0.17 nmol/liter, respectively. A significant decrease in catecholamine concentrations was observed only after 16 days of underfeeding. CONCLUSIONS: Clinically controlled underfeeding of patients with plurimetabolic syndrome may result in beneficial clinical and biochemical effects. The findings indicate that relatively long periods of underfeeding induce decreases in plasma catecholamine concentrations. Nevertheless, most of the fall in mean values in norepinephrine and also of the fall in blood pressure values occurred by Day 2. From those tendencies and from the significant changes in both parameters at Day 16 of severe underfeeding one could conclude that altered sympathetic nervous system activity could contribute to the fall in blood pressure.


Subject(s)
Epinephrine/blood , Fasting/physiology , Hyperlipidemias/physiopathology , Insulin Resistance/physiology , Norepinephrine/blood , Obesity/physiopathology , Sympathetic Nervous System/physiopathology , Adult , Blood Pressure/physiology , Energy Intake/physiology , Exercise Test , Female , Humans , Hyperlipidemias/diet therapy , Hypertension/physiopathology , Hypertension/therapy , Male , Middle Aged , Obesity/diet therapy , Syndrome
4.
Z Orthop Ihre Grenzgeb ; 137(3): 265-72, 1999.
Article in German | MEDLINE | ID: mdl-10441834

ABSTRACT

PROBLEM: Treadmill training with partial body weight support is a new promising technique in the rehabilitation in hip arthroplasty patients. With little data on the gait pattern and extent of pelvitrochanteric muscle activation, this study analysed the gait of hip arthroplasty patients walking on the treadmill and also during floor walking with and without crutches. METHOD: Gait analysis in 19 hip arthroplasty patients capable of full weight bearing included the assessment of kinematics, kinetics and kinesiologic electromyogram of relevant trunk and lower limb muscles during treadmill walking with 15% of body weight support, and during floor walking with and without crutches at comparable walking velocities. RESULTS: Both on the treadmill and with crutches, patients walked less frequent, with a longer stride and more symmetric as compared to the unaided gait. Both techniques, however, resulted in a reduced activation of most of the pelvitrochanteric muscles, particularly when using crutches. The comparison of both supporting methods revealed a higher activity of the M. gluteus medius of the affected side on the treadmill. The amount of body weight reduction was comparable ranging from 10 to 15%. CONCLUSIONS: Treadmill training with constant body weight support enables hip arthroplasty patient to entrain a dynamic and symmetric gait pattern with a better activation of the hip abductor of the affected side as compared to walking with crutches. Nevertheless, the level of activation was less than when walking without crutches which, however, resulted in a limping gait pattern.


Subject(s)
Arthroplasty, Replacement, Hip/rehabilitation , Crutches , Exercise Test , Gait/physiology , Osteoarthritis, Hip/surgery , Weight-Bearing/physiology , Aged , Aged, 80 and over , Electromyography , Female , Follow-Up Studies , Humans , Male , Middle Aged , Muscle, Skeletal/physiopathology , Postoperative Complications/physiopathology , Postoperative Complications/rehabilitation
5.
Clin Exp Hypertens ; 20(1): 41-52, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9507787

ABSTRACT

Enalapril combined with an extended-release formulation of diltiazem was evaluated in a 12-week multicenter trial of 112 patients with Stages 3-4 essential hypertension. Patients were randomized to once daily therapy with enalapril 5 mg plus diltiazem ER 120 mg or 180 mg. Dosages could be titrated and other antihypertensive agents added for blood pressure control. Efficacy was assessed with sitting blood pressures at trough (24 hours postdose). Overall, there was a decrease of -21.7/-18.4 mmHg. Patients responding to enalapril/diltiazem ER alone had a reduction of -15.0/-16.3 mmHg. Of all patients, 70% achieved a trough sitting diastolic blood pressure of < 95 mmHg. Common drug-related adverse experiences were headache, dizziness, rash, and asthenia/fatigue. This once daily fixed-combination of enalapril/diltiazem ER was generally well tolerated and effective when given alone or with other antihypertensives in Stage 3-4 hypertension.


Subject(s)
Antihypertensive Agents/therapeutic use , Diltiazem/therapeutic use , Enalapril/therapeutic use , Adult , Antihypertensive Agents/adverse effects , Diltiazem/adverse effects , Disease Progression , Drug Therapy, Combination , Enalapril/adverse effects , Evaluation Studies as Topic , Female , Humans , Male , Middle Aged
6.
Z Kardiol ; 85(3): 171-7, 1996 Mar.
Article in German | MEDLINE | ID: mdl-8659195

ABSTRACT

This is a report about the therapeutic behavior of blood pressure and heart rate in patients suffering from hypertension. Forty male patients with hypertension (age: 30-53 years) were treated either with running or swimming therapy according to the stamina principle or with nifedipine therapy (40-60 mg/d). Both groups were randomized. Peripheric hemodynamics were investigated by means of the Xenon-133-muscle-clearance (M. tibialis anterior). The values of interest were half-value time (T1/2) and the mean functional vessel diameter. Additionally total peripheric vascular resistance (TPR) and radiocardiographic cardiac output (CO) were measured. Significant decrease of systolic and diastolic blood pressure values at rest were obtained with the therapeutic regimens. CO increased and the TPR decreased. The decrease of blood pressure during physical therapy and with nifedipine therapy also is due to the enhanced microcirculation. Half-value time of muscle clearance (T1/2) and the mean functional vascular diameter were increased significantly.


Subject(s)
Calcium Channel Blockers/therapeutic use , Hypertension/rehabilitation , Nifedipine/therapeutic use , Physical Endurance , Running , Adult , Blood Pressure/drug effects , Blood Pressure/physiology , Calcium Channel Blockers/adverse effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Heart Rate/drug effects , Heart Rate/physiology , Hemodynamics/drug effects , Hemodynamics/physiology , Humans , Hypertension/physiopathology , Male , Microcirculation/drug effects , Microcirculation/physiopathology , Middle Aged , Nifedipine/adverse effects , Physical Endurance/physiology , Prospective Studies , Running/physiology , Swimming/physiology
7.
Phytomedicine ; 2(3): 205-7, 1996 Jan.
Article in English | MEDLINE | ID: mdl-23194617

ABSTRACT

The influence of daily application of coated garlic powder tablets (900 mg with an alliin content of 1.3% and an allicin content of 0.6%) on serum levels of malondialdehyde (MDA) and concentrations of reduced (GSH) and oxidized (GSSG) glutathione was investigated. 25 healthy volunteers were treated with garlic tablets for 2 months. After the 2 months' treatment a reduction of initial serum MDA level was observed. Application of Allium sativum reduced the MDA level by about 60% of the initial value. The MDA reducing effect was found in all age groups. In two age groups (younger than 30 years and older than 40 years) different initial values (higher values in elderly) but almost the equal MDA-levels after the treatment were found. The GSH concentration in circulating human erythrocytes showed a significant increase after the 2 month period of application of Allium sativum tablets, while the GSSG concentration showed no significant changes during the whole period of investigation. Thus a significantly decreasing trend of the GSSG: total glutathione ratio was measured.

8.
Clin Pharmacol Ther ; 56(2): 127-32, 1994 Aug.
Article in English | MEDLINE | ID: mdl-8062488

ABSTRACT

The objective of this study was to determine the potential role of circulating testosterone and estradiol in regulation of the activity of the sex-dependent pathways of propranolol metabolism (i.e., alpha-naphthoxylactic acid and propranolol glucuronide). The pharmacokinetics of a single 80 mg oral dose of propranolol and the plasma levels of the sex steroid hormones were therefore determined in normal volunteers. In 33 young men there was a positive correlation between the testosterone levels and the propranolol clearances through both alpha-naphthoxylactic acid (p < 0.001) and propranolol glucuronide (p < 0.002), as well as the total clearance (p < 0.05), but not through aromatic ring hydroxylation. Testosterone cypionate administration led to an increased clearance of propranolol through alpha-naphthoxylactic acid in nine of the 11 men studied, further supporting a stimulatory effect of testosterone on propranolol metabolism. In 23 young women there was no significant association between the circulating levels of either estradiol or testosterone and any of the clearances of propranolol. These observations may be clinically relevant for propranolol therapy and may provide improved insight into the influence of gender and circulating gonadal hormones on drug metabolism in humans.


Subject(s)
Estradiol/blood , Propranolol/pharmacokinetics , Testosterone/blood , Adult , Chromatography, High Pressure Liquid , Female , Humans , Lactates/metabolism , Male , Metabolic Clearance Rate , Oxidation-Reduction , Propranolol/administration & dosage , Propranolol/analogs & derivatives , Propranolol/metabolism , Sex Characteristics
9.
Br J Clin Pharmacol ; 37(1): 21-5, 1994 Jan.
Article in English | MEDLINE | ID: mdl-8148214

ABSTRACT

1. Plasma binding of tritium-labelled racemic propranolol (P) was measured by equilibrium dialysis. The unbound enantiomers were separated by h.p.l.c. after chiral derivatization. The binding of (-)-P was higher than that of (+)-P. 2. Contrary to previous suggestions, a sex difference in the plasma binding of the P enantiomers (9 young women, 12 young men) was not observed. The unbound percentage of (-)-P was 9.2 +/- 1.8 (mean +/- s.d.) in women vs 9.1 +/- 1.7 in men; for (+)-P it was 10.8 +/- 1.8 vs 10.8 +/- 2.1. 3. In the nine women, the binding did not change with fluctuating plasma oestradiol concentrations during the menstrual cycle. Testosterone cypionate doubled the circulating concentrations of testosterone in eight men but had no effect on P binding. 4. Ethinyl oestradiol (50 micrograms day-1) alone or together with norethindrone (OCD) in eight of the women produced an increase in the unbound percentage of both (-)-P (11.4 +/- 2.6 vs 9.5 +/- 1.6 for control; P < 0.001) and (+)-P (13.2 +/- 2.5 vs 11.2 +/- 1.5 for control; P < 0.001). This was due to a decrease in the plasma concentrations of alpha 1-acid glycoprotein from 0.54 +/- 0.11 mg ml-1 in control to 0.37 +/- 0.08 mg ml-1 (P < 0.001) during ethinyl oestradiol treatment. 5. Enantioselectivity in the unbound fraction of P increased with increasing total binding from a (-)/(+)-ratio of 0.93 at 84% binding to a (-)/(+)-ratio of 0.78 at 94% binding (P < 0.001).


Subject(s)
Estradiol/blood , Propranolol/blood , Sex Characteristics , Testosterone/blood , Adult , Chromatography, High Pressure Liquid , Drug Synergism , Estradiol/pharmacology , Ethinyl Estradiol/pharmacology , Female , Humans , Male , Menstrual Cycle , Middle Aged , Norethindrone/pharmacology , Propranolol/pharmacokinetics , Stereoisomerism , Testosterone/analogs & derivatives , Testosterone/pharmacology
10.
Xenobiotica ; 20(3): 321-31, 1990 Mar.
Article in English | MEDLINE | ID: mdl-2336841

ABSTRACT

1. The objective of this study was to determine the oral dose pharmacokinetics and metabolism of 4'-methylthiopropranolol (MTP) in man and compare the results with observations for propranolol in previous studies. 2. Three women and five men received single oral doses of MTP, dose range 5-320 mg. Plasma concentration of MTP over time were measured by gas chromatography-mass spectrometry. MTP metabolites in urine were identified by comparative high-performance liquid chromatographic (HPLC) retention times and mass spectrometry with previously characterized reference compounds and quantified by HPLC. 3. The oral clearance of MTP of 1.2-1.4 l/min for the 80, 160 and 320 mg doses was about one third of the value previously reported for propranolol. The half-life for MTP (3.3-4.1 h) was, however, similar to that of propranolol. In contrast to propranolol, the peak (2.5 h) plasma concentrations of MTP increased linearly with dose (5-320 mg). 4. The oral clearance for MTP was about 2-fold higher in the men than in the women (P less than 0.01). In addition, the clearance of the (S)-enantiomer was about 30% higher than that of the (R)-enantiomer (P less than 0.05), which was a reversal of that seen with propranolol. 5. The metabolism of MTP resulted mainly in sulphur oxidation to sulphoxide and sulphone metabolites. These two metabolites accounted for 75% of the MTP dose. This switching from aromatic carbon oxidation for propranolol to sulphur oxidation for MTP is proposed as the basis of the lower oral clearance of MTP. 6. This study also demonstrated higher plasma binding of MTP (unbound fraction 3.7%) than of propranolol (10.5%; P less than 0.01), a factor probably contributing to decreased tissue distribution of MTP.


Subject(s)
Propranolol/analogs & derivatives , Administration, Oral , Adult , Chromatography, High Pressure Liquid , Female , Gas Chromatography-Mass Spectrometry , Humans , Male , Metabolic Clearance Rate , Middle Aged , Propranolol/administration & dosage , Propranolol/metabolism , Propranolol/pharmacokinetics , Stereoisomerism
11.
Clin Pharmacol Ther ; 46(3): 257-63, 1989 Sep.
Article in English | MEDLINE | ID: mdl-2776391

ABSTRACT

This study determined the total clearance of propranolol and the partial clearances through each of its three primary metabolic pathways after administration of an 80 mg single oral dose in 28 young, white subjects (13 women; 15 men). The oral clearance of propranolol was significantly higher (63%, p less than 0.02) in the men (65.7 +/- 7.7 ml/min/kg; mean +/- SE) than in the women (40.2 +/- 6.2 ml/min/kg). This sex difference was mainly attributable to a 137% higher clearance through the P-450-mediated side-chain oxidation in the men (p less than 0.001). There was also a 52% higher clearance through glucuronidation in the men (p less than 0.02). In contrast, the clearance through the P-450-mediated ring oxidation was not different between men and women. After administration of simultaneous intravenous doses of hexadeuterium-labeled drug (0.1 mg/kg) to 11 of the subjects, there were no differences between men and women in volume of distribution or half-life. Moreover, there were no sex differences in plasma and blood binding of propranolol. This study thus demonstrates that higher plasma levels of propranolol occur in women than in men after oral doses and suggests that some drug metabolizing enzymes, but not others, are regulated by sex hormones in human beings.


Subject(s)
Propranolol/pharmacokinetics , Sex Characteristics , Administration, Oral , Adult , Biological Availability , Dose-Response Relationship, Drug , Female , Humans , Injections, Intravenous , Male , Propranolol/administration & dosage , Propranolol/blood
12.
Scand J Rehabil Med ; 21(1): 59-62, 1989.
Article in English | MEDLINE | ID: mdl-2711139

ABSTRACT

Eleven experiments were conducted on minipigs for the purpose of determining heat distribution in tissue exposed to therapeutic doses of microwaves. Temperatures were measured by means of coated thermocouples from the cutis, subcutis, musculature, and periost. Irradiation was applied to intensities of 10 W, 40 W and 60 W by means of a "Radarmed 12 S 251" circular emitter and to 60 W, 100 W and 140 W, using a trough emitter. Maximum temperature in superficial tissue layers was reached after five to ten minutes of microwave exposure. The temperature rise in the cutis and subcutis was steeper and at a higher rate than that in the muscles. Continuation of microwave irradiation did not cause any further rise in temperature, which was attributed to induction of hyperaemia. No difference regarding heat distribution was found to exist between pulsed and continuous irradiation at equal wattage.


Subject(s)
Body Temperature , Hyperthermia, Induced/veterinary , Microwaves/therapeutic use , Swine, Miniature/physiology , Animals , Models, Biological , Skin Temperature , Swine , Time Factors
13.
Am J Gastroenterol ; 83(10): 1158-60, 1988 Oct.
Article in English | MEDLINE | ID: mdl-3421227

ABSTRACT

Pancreatitis secondary to organophosphate insecticide toxicity is extremely rare. The few previously reported cases have resulted from oral ingestion of these agents. We present the first reported case of acute pancreatitis occurring after cutaneous exposure to an organophosphate insecticide. Symptoms of pancreatitis persisted for 6 months, followed by total resolution. The proposed mechanisms of pancreatic injury caused by organophosphate compounds are discussed.


Subject(s)
Cholinesterase Inhibitors/adverse effects , Insecticides/adverse effects , Organotin Compounds/adverse effects , Pancreatitis/chemically induced , Acute Disease , Adult , Cholangiopancreatography, Endoscopic Retrograde , Dimethoate/adverse effects , Environmental Exposure , Humans , Male , Pancreatitis/blood , Skin Absorption
14.
Clin Pharmacol Ther ; 44(4): 400-7, 1988 Oct.
Article in English | MEDLINE | ID: mdl-3168392

ABSTRACT

The influence of dietary sodium on the antihypertensive effects of verapamil and on components of sodium, water, and calcium metabolism was studied in nine white patients 50 to 65 years old with normal renin hypertension. Diets consisting of 109 and 259 mEq Na were given for 5 days each before the study drug was given. On days 4 and 9, intravenous verapamil (0.075 mg/kg) and oral verapamil (80 mg) were given, followed by 80 mg at 8-hour intervals for three doses. On days 1, 4, 5, 9, and 10, serum and urine electrolytes, osmolality (urine [Uosm], serum [Sosm], and osmolar clearance [Cosm]), calcium plasma renin activity (PRA), and levels of serum aldosterone, 1,25-hydroxyvitamin D, serum ionized calcium, parathyroid hormone, atrial natriuretic hormone (atriopeptin), and erythrocyte calcium and electrolytes were measured. On days 5 and 10, serial plasma samples for measurement of verapamil and norverapamil levels were drawn immediately after the last oral dose of verapamil. After verapamil, Uosm and Cosm decreased during both 109 and 259 mEq sodium diets (Uosm, p less than 0.025; Cosm, p less than 0.01 and p less than 0.025, respectively), but free water clearance increased during each diet (p less than 0.01). Urine volume and sodium excretion increased with the 259 mEq sodium diet (p less than 0.025 and p less than 0.01, respectively). There were no significant changes in measured values of components of calcium metabolism with either diet or after verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Diuresis/drug effects , Natriuresis/drug effects , Sodium, Dietary/administration & dosage , Verapamil/pharmacology , Adult , Blood Pressure/drug effects , Body Weight/drug effects , Calcium/metabolism , Female , Humans , Male , Middle Aged , Pulse/drug effects , Verapamil/pharmacokinetics
15.
Z Gesamte Inn Med ; 43(12): 328-30, 1988 Jun 15.
Article in German | MEDLINE | ID: mdl-3062930

ABSTRACT

Based on the definition of physiotherapy as having functional orientation aiming to stimulate reactive processes of body itself, the position of physiotherapy is outlined. The most important methods for the treatment of the bronchitic syndrome are described. Their mode of action, target, and dose are explained. In practice, physiotherapy should be applied as a complex series of treatment.


Subject(s)
Lung Diseases, Obstructive/rehabilitation , Physical Therapy Modalities/methods , Bronchitis/rehabilitation , Humans
16.
Z Gesamte Inn Med ; 42(23): 676-80, 1987 Dec 01.
Article in German | MEDLINE | ID: mdl-3445651

ABSTRACT

The use of physiotherapy as traditionally successful form of therapy is not in the least satisfying in practice. The reasons for this are explained. Issuing from a general assessment of the therapy in the system medical care, principal aspects for an interdisciplinary therapy are demonstrated. Essential for a scientifically proved use of physiotherapy is the differentiation between general and specific aspects in the pathologic process made in the general nosology. The effects of the physiotherapy are shown and its significance as basis therapy is emphasized. Apart from the knowledge of the individual physiotherapeutic remedies, the use of the physiotherapy has as its prerequisite a valuation of the pathogenetic factors and actual additional conditions. Corresponding to the therapeutic aim, the physiotherapy should be conceived either as monotherapy or as a long-term, frequently multi-dimensional therapeutic programme. Essential errors in practice are the technically insufficient and inconsequent use of the treatment capacities. With the help of the recommendations for the use of the physiotherapy in the essential hypertension and rheumatoid arthritis ways are indicated how the potencies of the specialty are to be realised better than hitherto done in chronic diseases.


Subject(s)
Physical Therapy Modalities/methods , Arthritis, Rheumatoid/rehabilitation , Combined Modality Therapy , Humans , Hypertension/rehabilitation
17.
J Pharmacol Exp Ther ; 241(3): 928-33, 1987 Jun.
Article in English | MEDLINE | ID: mdl-3598909

ABSTRACT

The objective of this study was to examine the effect of cigarette smoking on the activities of the three primary pathways governing propranolol metabolism in human subjects, i.e., glucuronidation, side-chain oxidation and ring oxidation. A single 80-mg dose of propranolol p.o. together with 40 muCi of 4-[3H]propranolol was given to six smoking and seven nonsmoking, young, white, male subjects and the oral clearance of propranolol and the partial clearances through these pathways were determined. The oral clearance of propranolol was increased by 77% (P less than .02) in smokers compared with nonsmokers. This apparent induction of propranolol metabolism was due to a 122% increase in side-chain oxidation (P less than .001) and a 55% increase in glucuronidation (P less than .01). There was no significant effect of smoking on aromatic ring oxidation. Smokers had a 30% greater renal clearance of total metabolites (P less than .05), due mainly to a 53% greater renal clearance of the acidic propranolol metabolite naphthoxylactic acid (P less than .001). These data show a selective effect of smoking on propranolol metabolism and suggest that side-chain oxidation and glucuronidation are mediated by isoenzymes inducible by aromatic hydrocarbons. The selective effect of smoking on the renal clearance of the major propranolol metabolite naphthoxylactic acid may be due to induction of a renal transport protein.


Subject(s)
Kidney/metabolism , Propranolol/metabolism , Smoking , Adult , Creatinine/metabolism , Half-Life , Humans , Lactates/metabolism , Male , Metabolic Clearance Rate , Propranolol/analogs & derivatives
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