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Biomedical subjects

B Mangold

Publications and source records attributed to B Mangold.

At least 19 recordsLinked to original sources
PubMed2001

Omapatrilat in patients with hepatic cirrhosis. Pharmacodynamics and pharmacokinetics.

OBJECTIVE: The pharmacodynamics and pharmacokinetics of omapatrilat, a member of a new class of cardiovascular compounds, the vasopeptidase inhibitors, were evaluated in subjects with hepatic cirrhosis (n = 10) and in healthy subjects (n = 10) matched for age, weight, gender and smoking history. METHODS: All subjects received omapatrilat 25 mg orally once daily for 14 days. Plasma renin and urinary atrial natriuretic peptide (ANP) levels were measured to assess the effect of omapatrilat on cirrhotic subjects. The effect of omapatrilat on blood pressure as well as changes in ANP and plasma renin levels were not altered by hepatic impairment. Pharmacokinetic parameters were determined from plasma omapatrilat concentrations. RESULTS: There were no significant differences between the two subject groups with regard to log-transformed area under the curve or maximum observed plasma concentration. Systemic accumulation was similar in the two groups. CONCLUSION: These results suggest, based on findings in otherwise healthy cirrhotic subjects, that no adjustment of standard dosing regimens is indicated for hypertensive patients with mild to moderate cirrhosis.

Administration, Oral↗
PubMed2000

[SIDS prevention program in Tyrol].

In April 1994, an intervention campaign to reduce the incidence of sudden infant death syndrome (SIDS) was established in the Tyrol. The campaign was intended to increase knowledge concerning risk factors for SIDS in the general community and to improve individual care for infants at risk. In contrast to interventional programmes in other federal states of Austria (i.e. Vorarlberg, Styria), this programme did not utilise polysomnography for identifying infants at risk. A part of the intervention programme was the "Styrian risk questionnaire", a standardised questionnaire concerning risk factors for SIDS. Individual instructions for health care of children at risk (risk score > or = 7) were provided and, if necessary, subscription of home monitoring was performed at the out-patient department (SIDS out-patient service) of the Department of Paediatrics in Innsbruck and other paediatric departments throughout the Tyrol. The educational programme also included information concerning basic life support. Psychological support was offered to parents of SIDS infants. Risk factors for SIDS in the Tyrol before the campaign were assessed in a retrospective case-control study (time period 1984-1994; 99 SIDS infants, 136 controls). The risk of SIDS was markedly reduced when parents had detailed knowledge of the risk factors of SIDS (odds ratio (OR) 0.03; p < 0.001), which emphasises the importance of information and educational programmes. The incidence of SIDS declined after the beginning of the intervention campaign from 1.83/1000 live births (average incidence from 1984-1994) to 0.4/1000 live births and remained at this level thereafter. Post-neonatal mortality also declined from 3.9 to 1.3/1000 live births. The prevalence of the prone sleeping position declined immediately after the campaign (53.7% vs. 5.4%, p < 0.001), as did the frequency of maternal smoking during pregnancy (22.9% vs. 14.5%, p < 0.01). Breast feeding became more popular. In all, the low-cost intervention programme in the Tyrol proved to be highly efficient in reducing the risk of SIDS and in maintaining this effect for several years.

Adult↗
PubMed2000

Comparison of the pharmacokinetics of fosinoprilat with enalaprilat and lisinopril in patients with congestive heart failure and chronic renal insufficiency.

AIMS: To compare the serum pharmacokinetics of fosinoprilat with enalaprilat and lisinopril after 1 and 10 days of dosing with fosinopril, enalapril and lisinopril. METHODS: Patients with congestive heart failure (CHF, NYHA Class II-IV) and chronic renal insufficiency (creatinine clearance </=30 ml min-1 ) were randomized to receive fosinopril, enalapril or lisinopril in two parallel-group studies. In the first study 24 patients were treated with 10 mg fosinopril (n=12 patients) or 2.5 mg enalapril (n=12) every morning for 10 consecutive days. In the second study 31 patients were treated with 10 mg fosinopril (n=16 patients) or 5 mg lisinopril (n=15) every morning for 10 consecutive days. Samples of blood were collected for determination of pharmacokinetic parameters. The area under the curve (AUC) between the first and last days of treatment and the accumulation index (AI) were the primary outcome measures. RESULTS: All three angiotensin converting enzyme (ACE) inhibitors exhibited a significant increase in AUC between the first and last days of treatment in both studies. The difference between the AI for fosinoprilat (1.41) and enalaprilat (1.96) was statistically significant (95% CI: 1.05, 1.84). Similarly, the difference between the AI for fosinoprilat (1.21) and lisinopril (2.76) was statistically significant (95% CI: 1.85, 2.69). All three ACE inhibitors completely inhibited serum ACE for 24 h. All treatments were well tolerated. CONCLUSIONS: Fosinoprilat exhibits significantly less accumulation than enalaprilat or lisinopril in patients with CHF and renal insufficiency, most probably because fosinoprilat is eliminated by both the kidney and liver, and increased hepatic elimination can compensate for reduced renal clearance in patients with kidney dysfunction.

Adolescent↗
PubMed2000

Pharmacokinetics of single-dose oral stavudine in subjects with renal impairment and in subjects requiring hemodialysis.

Two open-label studies assessed the pharmacokinetics of single orally administered doses of 40 mg of stavudine in subjects with renal impairment. In one study (study I), 15 subjects with selected degrees of renal impairment, but not requiring hemodialysis, were stratified into three groups of five subjects each according to creatinine clearance (CL(CR)) normalized by body surface area (ml/min/1.73 m(2)): mild (CL(CR), 60 to 80), moderate (30 to 50), and severe (</=20) renal impairment. Five healthy subjects (CL(CR) >/= 90) were also enrolled. The stavudine area under the curve from 0 h to infinity (AUC(0-infinity)) increased nonlinearly with declining renal function: 1,864, 2,215, 3,609, and 5,928 ng. h/ml for normal renal function and for mild, moderate, and severe renal impairment, respectively (P = 0.0001 between renal impairment groups). The following stavudine dosage recommendations for renal impairment were proposed for subjects weighing >/=60 kg: CL(CR) of >50 ml/min/1.73 m(2), 40 mg every 12 h; CL(CR) of 21 to 50 ml/min/1. 73 m(2), 20 mg every 12 h; and CL(CR) of 10 to 20 ml/min/1.73 m(2), 20 mg every 24 h. For subjects weighing <60 kg, the proposed doses were 30, 15, and 15 mg, respectively, with the same dosing intervals specified above. In a second study (study II), 12 subjects with end-stage renal disease requiring hemodialysis three times a week were enrolled in a randomized, open-label crossover study (dialysis 2 h after dosing and lasting 4 h or dosing without dialysis). There were no statistically significant differences for AUC(0-infinity), AUC(2-6), time to maximum concentration of drug in serum, half-life, or apparent oral clearance when the two treatment dosage regimens were compared. As a result of study II, the recommended dosing rate for subjects requiring hemodialysis was the same as that proposed for those with severe renal impairment not requiring hemodialysis; however, dosing was recommended to follow hemodialysis and to occur at the same time each day.

Administration, Oral↗
PubMed1999

Irbesartan does not affect the steady-state pharmacodynamics and pharmacokinetics of warfarin.

OBJECTIVES: To determine whether the initiation or titration of irbesartan alters the pharmacodynamics and/or pharmacokinetics of warfarin in a clinically significant manner, thereby requiring additional monitoring of the anticoagulant effect of warfarin. METHODS: Daily doses of warfarin were administered to 16 healthy males for 21 days (10 mg on day 1 and 2.5-10 mg on days 2-21). Irbesartan (300 mg/day) or placebo was concomitantly administered on days 15-21. The pharmacodynamic parameters prothrombin time (PT) and prothrombin time ratio (PTR) were evaluated throughout the study. Plasma and urine samples were collected before and up to 24 h after administration on days 14, 15 and 21 for the determination of the maximum concentration (C(max)), time to reach C(max)(t(max)), the area under the concentration-time curve (AUC) of S-warfarin and the cumulative urinary excretion of warfarin and its metabolites. Pre-dose plasma samples were also collected to determine the C(min) of S-warfarin (days 12, 13, 14 and 21) and irbesartan (days 19, 20 and 21). RESULTS: Analysis of PTR data revealed no significant difference between the group mean PTR values at day 22 and those at day 15 (P=0.699). S-warfarin concentrations in plasma and urine, as well as the urinary concentrations of the metabolites of warfarin, were not affected by concomitant single- or multiple-dose administration of irbesartan. Plasma C(min) concentrations of S-warfarin and irbesartan were also not affected. CONCLUSIONS: No clinically important effect of irbesartan on the pharmacodynamics and pharmacokinetics of warfarin are likely to occur during concomitant administration; therefore, neither a dosage adjustment of irbesartan or warfarin nor any additional monitoring of the anticoagulant effect of warfarin is necessary.

Adolescent↗
PubMed1999

Pharmacodynamic effects of dual neutral endopeptidase-angiotensin-converting enzyme inhibition versus angiotensin-converting enzyme inhibition in humans.

BACKGROUND: There is currently no clear evidence that dual neutral endopeptidase-angiotensin-converting enzyme inhibitors have effects on angiotensin-converting enzyme, renin, or blood pressure that are different from specific angiotensin-converting enzyme inhibitors in humans. METHODS AND RESULTS: In a double-blind, placebo-controlled crossover study, single oral doses of the dual neutral endopeptidase-angiotensin-converting enzyme inhibitor, 10 mg BMS-186716 and the angiotensin-converting enzyme inhibitor fosinopril (20 mg) were administered to 9 normotensive subjects with induced mild sodium depletion. Values for area under the time curve from 0 to 24 hours [AUC(0-24)] for the plasma angiotensin II/angiotensin I ratio and for angiotensin II were similar for 10 mg BMS-186716 and 20 mg fosinopril. Plasma atrial natriuretic peptide decreased significantly after 20 mg fosinopril (9+/-3 pg/mL; P < .05 versus 10 mg BMS-186716 and placebo) compared with 10 mg BMS-186716 (16+/-5 pg/mL) and placebo (16+/-5 pg/mL). BMS-186716, 10 mg, significantly increased urinary atrial natriuretic peptide from baseline by 2+/-1.3-fold (P < .05 versus placebo and 20 mg fosinopril). AUC(0-24) of plasma active renin did not differ significantly between 10 mg BMS-186716 (3898+/-333 pg x h x mL(-1)) and 20 mg fosinopril (4383+/-302 pg x h x mL(-1); difference not significant). Both drugs decreased blood pressure, but the AUC(0-24) of the changes in mean blood pressure differed significantly from placebo (79+/-84 mm Hg x h) only for 20 mg fosinopril (181+/-6 mm Hg x h; P < .05) but not for 10 mg BMS-186716 (118+/-7 mmHg x h). CONCLUSIONS: In this model, single oral doses of 10 mg BMS-186716 and 20 mg fosinopril induced similar 24-hour in vivo angiotensin-converting enzyme inhibition. BMS-186716, 10 mg, increased urinary atrial natriuretic peptide and blunted the expected decrease in plasma atrial natriuretic peptide caused by angiotensin-converting enzyme inhibition. BMS-186716, 10 mg, did not inhibit plasma active renin rise compared with 20 mg fosinopril. A single oral dose of 10 mg BMS-186716 had a shorter blood pressure-lowering effect than 20 mg fosinopril.

Administration, Oral↗
PubMed1999

Fosinopril/hydrochlorothiazide: single dose and steady-state pharmacokinetics and pharmacodynamics.

AIMS: Fosinoprilat, the active product of fosinopril, is eliminated by an hepatic pathway in addition to the renal pathway shared by other angiotensin converting enzyme inhibitors (ACEIs). This study aimed to determine whether impaired renal function affects the pharmacokinetics and pharmacodynamics of a combination of fosinopril and hydrochlorothiazide (HCTZ). METHODS: The study had a parallel-group design comparing patients with renal impairment and body-mass-index-matched normal controls. The study was done in a University clinic in 13 patients with renal impairment (mean creatinine clearance 55.7+/-15.6 ml min-1 1.73 m-2 ) and 13 age-, sex-, and body-mass-index-matched normal controls (mean creatinine clearance 102.4+/-8.9 ml min-1 1.73 m-2 ). All patients and normal controls received fosinopril sodium 20 mg and HCTZ 12.5 mg as a daily oral administration on days 1-5. Non-compartmental pharmacokinetic parameters of fosinoprilat and HCTZ were determined from blood and urine samples obtained over 48 h starting on Day 1 (single dose) and Day 5 (steady state): maximum serum concentration (Cmax ), time to maximum serum concentration (tmax ), area under the serum concentration-time curve during the dosing interval (AUC), cumulative urinary excretion (CUE) and the accumulation index (AI; ratio of AUC-day 5/AUC-day 1). Pharmacodynamic parameters were also measured over 24 h on day 1 and over 48 h on day 5: serum ACE activity and arterial blood pressure. RESULTS: Fosinoprilat pharmacokinetic parameters on day 1 in renally impaired vs normal patients: Cmax=387+/-0.19 vs 324+/-0.25 ng ml-1 (P=0.07); tmax=3.5 vs 3.0 h (P=0.58); AUC=3510+/-0.29 vs 2701+/-0.35 ng ml-1 h (P=0. 072); CUE=5.08+/-2.70 vs 7.40+/-2.56% (P=0.009). Fosinoprilat parameters on day 5: Cmax=517+/-0.40 vs 357+/-0.19 ng ml-1 (P=0. 007); tmax=3.0 vs 3.0 h (P >0.99); AUC=4098+/-0.43 vs 2872+/-0.30 ng ml-1 h (P=0.027); CUE=6.81+/-3.53 vs 8.10+/-2.80% (P=0.068). AI=1. 17+/-0.33 vs 1.06+/-0.23 (P=0.29). In both groups ACE inhibition and blood pressure response were similar over 24 h and slightly greater 48 h after last dosing. CONCLUSIONS: In renally impaired subjects fosinopril and HCTZ can be coadministered without undue increases in fosinoprilat concentrations or any clinically significant pharmacodynamic effects. This is probably due to the dual excretory pathways for fosinoprilat.

Adolescent↗
PubMed1997

Accumulation of lovastatin, but not pravastatin, in the blood of cyclosporine-treated kidney graft patients after multiple doses.

OBJECTIVES: To study pravastatin and lovastatin pharmacokinetic and pharmacodynamic effects and their interactions with cydosporine (INN, ciclosporin) in kidney transplant patients after single and multiple doses. SUBJECTS AND METHODS: The pharmacokinetic and pharmacodynamic effects of administration of 20 mg/day oral pravastatin and lovastatin for 28 days and their interactions with cyclosporine (2 to 6 mg/kg/day) were studied in a double-blind, double-dummy, randomized, parallel-group multicenter trial in 44 stable kidney graft recipients. RESULTS: The median area under the curve [AUC(0-24)] of pravastatin was 249 microg x hr/L (range, 104 to 1026 microg x hr/L) after a single dose (day 1) and 241 microg x hr/L (114 to 969 microg x hr/L) after multiple doses (day 28) and was fivefold higher than values reported in the absence of cyclosporine. The median AUC(0-24) of lovastatin was 243 microg x hr/L (105 to 858 microg x hr/L) on day 1 and 459 microg x hr/L (140 to 1508 microg x hr/L) on day 28. Besides a significant accumulation during the study period (p < 0.001), the lovastatin AUC(0-24) values were twentyfold higher than values reported without cyclosporine. Coadministration of pravastatin or lovastatin did not alter cyclosporine pharmacokinetics. In this study, 20 mg/day doses of both drugs resulted in a significant improvement of the lipid profile and were well tolerated. CONCLUSIONS: In contrast to lovastatin, pravastatin did not accumulate over the study period, which is probably one of the reasons rhabdomyolysis has been reported in lovastatin-treated but not pravastatin-treated transplant patients receiving cyclosporine immunosuppression.

Adult↗
PubMed1992

[Organization of the psychotherapy-psychosomatic department and its integration into the University Pediatric Clinic].

With regard to the 20 years history of our psychotherapeutic unit some essential feed-back-loops between medical pediatric work and our systemic thinking are presented. So-called objective tasks interfere with group dynamics and subjective task formulations. If two models (the biomedical and the systemic-therapeutic) collide, both of them get "contaminated" and should be changed in a co-evolutive process--for the sake of the patients and their families. In our experience this is only possible, if autonomy of the unit is present, then the unit can wait for "perturbations".

Austria↗
PubMed1991

[The biological availability of cefadroxil given simultaneously with N-acetylcysteine].

A preliminary study revealed that similarly to the antibiotics amoxillin, thiamphenicol, erythromycin and doxycycline, the oral cephalosporin cefadroxil (CAS 66592-87-8) can be administered simultaneously with the mucolytic n-acetylcysteine (CAS 616-91-1). In the present study 12 healthy male volunteers received in a randomised cross-over design a single oral dose of 1000 mg cefadroxil or a single oral dose of 1000 mg cefadroxil (Bidocef) plus 200 mg n-acetylcysteine. The two study days were separated by a wash-out period of one week. To determine the pharmacokinetic profile of cefadroxil, plasma and sputum were analysed by HPLC at defined intervals. Regarding the bioavailability of cefadroxil, the free combination is bioequivalent to the individual component. After administration of cefadroxil plus n-acetylcysteine, a higher cefadroxil concentration was found in the sputum compared to an administration of cefadroxil alone. However, the difference was not statistically significant. According to the results, simultaneous administration of the oral cephalosporin cefadroxil and the mucolytic n-acetylcysteine is possible without changes in the bioavailability of cefadroxil being observed.

Acetylcysteine↗
PubMed1990

Pharmacokinetics and absolute bioavailability of ibuprofen after oral administration of ibuprofen lysine in man.

The lysine salt of d,l-2-(4-isobutylphenyl)-propionic acid (ibuprofen lysine) was administered as a single oral dose of 500 mg by means of commercially available coated tablets (Imbun).* To assess the absolute bioavailability of ibuprofen after its oral application as a lysine salt, intravenous injections of ibuprofen solutions containing 200 mg and 400 mg of the drug served as reference application. In a partially randomized cross-over design, 8 healthy male volunteers received three different single dose administrations which were separated by wash-out periods of 4 days each. Ibuprofen plasma concentrations were determined by HPLC using direct injection, pre-column enrichment and column switching techniques. From the results of intravenous injections one can deduce linear ibuprofen pharmacokinetics within the considered dosage range, with corresponding AUC0-infinity values of 3786 micrograms * min ml-1 and 7260 micrograms * min ml-1 for the 200 mg and 400 mg doses, respectively. The values of plasma clearances as well as those of different volumes of distribution showed remarkable constancy after evaluation from both intravenous injections. The absorption of orally administered ibuprofen lysine proved to be rapid, resulting in a mean peak plasma level (Cmax) of 31 micrograms ml-1 ibuprofen and in a mean time to peak (tmax) of 45 min. The absolute bioavailability of ibuprofen amounts to 102.7 per cent, indicating a complete absorption of ibuprofen when administered as its lysine salt. Drug tolerability was excellent for the oral administration of ibuprofen lysine as well as for the intravenous treatments with ibuprofen free acid. Only mild and transient adverse drug reactions such as mild burning or dragging sensation during injection or mild redness at the site of injection were reported.

Administration, Oral↗
PubMed1990

[Computer-assisted analysis of the tocogram. Initial experience using a new evaluation procedure].

This paper describes first observations with a new computer aided analysis of tocogram. It seems that length of uterine contraction is an important parameter for quality of labour. In 9 from 12 cases promotion to constant length of labour with relatively low absolute duration of contractions was connected with a distinct increase of the velocity of cervical dilatation. The uniformity can be an important factor for the conversion into active phase of labour.

Adolescent↗
PubMed1990

[Effects of systemic family therapy on the organization and operation of a pediatric psychotherapy unit].

This article communicates novel criteria for the necessity of stationary psychotherapy in children and adolescents derived from practice in systemic family-therapy. Discussion of advantages and disadvantages of stationary psychotherapy from a systemic versus individual centered perspective results in different conclusions. Originating from this discussion important factors implicating preparations and planning for stationary psychotherapy are analyzed.

Adolescent↗
PubMed1989

[Human pharmacologic studies on transdermal administration of mepindolol. Pharmacodynamic and orienting pharmacokinetics].

The pharmacodynamic effects of acute and repeated application of a transdermal patch (BIO TSD) containing 20 mg of the beta-receptor blocking agent mepindolol were assessed in 13 normotensive male volunteers. Orienting measurements of mepindolol serum levels were performed additionally. At rest, the effects on blood pressure and heart rate were very limited. However, during submaximum ergometer exercise, significant systemic beta-blocking effects were observed, especially after 5 days treatment. Repeated administration did not induce tachyphylaxis but resulted in an enhanced efficacy. The mepindolol serum concentrations were markedly lower than those measured after oral application of the drug. No systemic or local adverse reactions nor any relevant changes in laboratory parameters were observed.

Administration, Cutaneous↗
PubMed1987

[Pediatric psychosomatic medicine: where did we come from? What is our status? Where are we going?].

Historical development of pediatric psychosomatics from psychodiagnostics to individual-centered psychotherapy and recently to family oriented and systemic therapy is outlined in the example of our own development and that of our department. In classical psychosomatics dualism in medicine is kept alive by considering only so-called "psychosomatic diseases". At present, there is need for a new and more complex model in medicine: The bio-psycho-social model in medicine puts emphasis on diagnosis and treatment of psychological and social factors in the genesis, course and outcome of every disease. Especially in pediatrics this model should be favored. Some consequences for treatment, research and medical education are proposed. Finally we touch on the new potentials of systemic family therapy.

Austria↗