[Detection of impaired renal function: is the modern serologic marker cystatin C more accurate than the 99mTc-MAG3 clearance?]. / Nachweis der eingeschränkten Nierenfunktion: Ist der moderne serologische Marker Cystatin C der 99mTc-MAG3-Clearance überlegen?

AIM: Renal function is usually determined by means of creatinine-clearance, and of serum Cystatin C, the latter with increasing frequency. The present study analyses, whether the diagnostic accuracy of (99m)Tc-MAG(3) clearance is comparable to that of these modern serologic methods. PATIENTS, METHODS: 71 consecutive adult Caucasian patients (42 female, 29 male; age 50 +/- 16 yrs., range 20-83) who were referred to a nuclear medicine department for determination of bilateral renal function with (99m)Tc-MAG(3) were included. Following sufficient hydration, 10 ml of blood were taken for determination of Cystatin C and creatinine in serum prior to i.v. injection of the radiotracer. According to the recommendations of the National Kidney Foundation, glomerular filtration rate (GFR) was calculated from serum creatinine using either Cockcroft & Gault and Modification of Diet in Renal Disease (MDRD) study equation. These estimates of GFR served as reference. Cystatin C is a low molecular protein produced by all nuclear cells and is eliminated to 85 % by glomerular filtration. Analysis of (99m)Tc-MAG(3) clearance was performed by means of Bubeck's formula. RESULTS: Linear regression analysis produced Pearson's correlation coefficients of r = 0.68 and r = -0.69 for the comparison of either Cystatin C and (99m)Tc-MAG(3) clearance with the Cockcroft & Gault equation. The comparison of Cystatin C and (99m)Tc-MAG(3) clearance with MDRD study equation resulted in correlation coefficients of r = 0.755 and r = -0.77. None of these differences were significant. The exclusion of renal impairment or the detection of an at least moderate renal impairment revealed again no significant differences between Cystatin C and (99m)Tc-MAG(3) clearance. CONCLUSIONS: Cystatin C and (99m)Tc-MAG(3) clearance are equally suited to exclude renal impairment or to detect a relevant renal impairment. Differences between both procedures are more likely a result of the applied reference method.

The influence of age on the pharmacokinetics of nimodipine.

Single and multiple dose pharmacokinetics and absolute bioavailability of the calcium antagonist nimodipine (Nimotop) were investigated in 24 young (age: 22 - 40 years) and 24 elderly (age: 59 - 79 years) healthy subjects. There were no significant changes in blood pressure, heart rate, and ECG-parameters in both age groups, and no increase in frequency of adverse events was observed in the elderly. Following a single intravenous infusion of 15 micrograms/kg for 1 hour, there were no significant differences in nimodipine pharmacokinetics between young and elderly volunteers. Oral administration (single dose of 30 mg, 30 mg t.i.d. for 6 days), however, resulted in pronounced differences in AUC and Cmax between elderly and young subjects when the same doses were given. Under steady-state conditions the elderly reached significantly higher Cmax (g.mean/SD: 23.3/1.62 micrograms/l) and AUC-values (47.5/1.62 micrograms*h/l) than the young volunteers (13.5/2.03 micrograms/l, and 25.7/1.73 micrograms*h/l, respectively). The absolute bioavailability was 10.6/1.60% in the elderly and 5.4/2.11% in young subjects. The observed pharmacokinetic differences in the study most likely reflect the reduced metabolic clearance of nimodipine in the elderly.

Determination of furosemide in plasma and urine by gas chromatography/mass spectrometry.

A new method for the determination of furosemide (CAS 54-31-9) in plasma and urine by gas chromatography/mass spectrometry (GC/MS) has been developed. After acidification the samples were extracted by ethyl acetate and methylated by methyl iodide. The chromatography was carried out on a fused-silica capillary column with SE-54 stationary phase. Detection was performed by selected ion monitoring (ions 81 and 372 were monitored for furosemide and ions 363 and 406 for internal standard bumetanide). Limit of quantitation was 10 ng/ml for plasma and 40 ng/ml for urine and the calibration curves were linear up to 100,000 ng/ml.

Pharmacokinetics of reboxetine in healthy volunteers. Single oral doses, linearity and plasma protein binding.

The pharmacokinetics of reboxetine, a new antidepressant agent, were found to be close to linear in a crossover study comparing administration of single 2, 3, 4, and 5 mg capsule doses in 15 healthy male volunteers, and in the same study the capsules were bioequivalent to the proposed therapeutic tablet formulation (4 mg). Kinetic analysis was based on HPLC assay of reboxetine in plasma and urine collected up to 72 h after each administration. Plasma levels indicated a rapid absorption (tmax approximately equal to 2 h) and an elimination half-life of about 13 h. Clearance and volume of distribution were modest (ratios to bioavailability: CL/F approximately equal to 29 mL min-1; Vz/F approximately equal to 32 L); urinary excretion was approximately 9% of dose, corresponding to a renal clearance of only 3 mL min-1 (a value consistent with the rate of glomerular filtration of unbound drug). In vitro, binding to plasma proteins, estimated from radioactivity levels following dialysis of 14C-labelled reboxetine, appeared to be dominated by alpha 1-acid glycoprotein without marked saturation up to plasma concentrations of over 500 ng mL-1 (2.8-3.1% unbound with human plasma from three additional volunteers; 1.8-2.0% for 2 gL-1 orosomucoid alpha 1-acid glycoprotein, and 46.4-47.4% for 40 g L-1 albumin), whilst the mean Cmax in the current study was much lower (164 ng mL-1 after a 5mg dose).

Pharmacokinetic interactions between lithium and fluoxetine after single and repeated fluoxetine administration in young healthy volunteers.

Pharmacokinetic interactions following coadministration of fluoxetine and lithium were investigated in 10 young healthy subjects. Both drugs were administered orally in a non-blinded design with 3 consecutive treatment periods: single oral dose of lithium (32.4 mmol lithium as acetate, Quilonum; coadministration of single oral doses of lithium (32.4 mmol) and fluoxetine (Fluctin, 60 mg); and single oral dose of lithium after 7-day pretreatment with fluoxetine (20 mg t.i.d.). Periods 1 and 2 were separated by a 1-week washout phase, while period 3 followed on immediately after period 2. Lithium serum concentrations were practically identical in periods 1 and 3 (administration of lithium alone and after chronic fluoxetine dosing). However, in period 2, when the 2 drugs were coadministered as single oral doses, the lithium concentrations were lower in the first 4 hours after medication compared with treatment periods 1 and 3. Cmax was also significantly lower in period 2. The times to peak, however, were not significantly changed by any fluoxetine comedication. The parameters AUC0 --> infinity, t1/2, total clearance (Cltot) and renal clearance (Clren) determined after administration of lithium alone did not differ statistically from values determined after single or after repeated fluoxetine dosing. Coadministration of lithium and fluoxetine did not produce any clinically relevant changes in hemodynamics, ECGs or laboratory parameters. After single doses of both drugs the most frequently reported symptoms were gastrointestinal complaints, while mild sedative symptoms were predominant when lithium was given after repeated fluoxetine medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Steady-state pharmacokinetics of nimodipine during chronic administration of indometacin in elderly healthy volunteers.

The possible influence of chronic indometacin (CAS 53-86-1) medication on nimodipine (CAS 66085-59-4) pharmacokinetics was investigated in 24 elderly healthy subjects. Both drugs were orally administered in a non-blinded, randomized, twofold crossover design. The study periods with a 5-day treatment each were separated by a 2-week washout period. The Css,max of nimodipine was increased after the combined administration of nimodipine (30 mg t.i.d.) and indometacin (25 mg b.i.d.) as compared with those after nimodipine monotherapy: 24.2 +/- 14.7 micrograms/l vs. 19.7 +/- 10.3 micrograms/l. This increase, however, was not of an order to become clinically relevant. Nimodipine AUCss slightly increased under indometacin co-medication from 57.9 +/- 27.5 micrograms.h.l-1 to 62.8 +/- 26.6 micrograms.h.l-1, resulting in a mean relative bioavailability of nimodipine of 111% with a 90%-confidence interval of 96-128% for the combined medication. There was no evidence of any clinically relevant difference in hemodynamics and other findings between both treatments. The overall frequency of side effects was low after both medication regimens. The findings of this study indicate that a combined treatment with both compounds should not be associated with a clinically relevant interaction.

Chronic administration of nimodipine and propranolol in elderly normotensive subjects--an interaction study.

Nimodipine (30 mg t.i.d.) and propranolol (40 mg t.i.d.) were given orally to 24 healthy elderly subjects in a randomized, un-blinded, threefold crossover study. Each of the study periods lasted 8 days with a 5-day treatment phase separated by 2-week washout phases. Mean peak nimodipine plasma concentration was decreased after combined administration of the two drugs (16.1 +/- 8.1 micrograms/l vs. 12.4 +/- 9.5 micrograms/l). Nimodipine AUCss slightly decreased under propranolol co-medication from 44.9 +/- 15.1 micrograms x l/l to 38.8 +/- 22.5 micrograms x h/l, resulting in an AUC ratio of 88.8 +/- 44.5%. The relative bioavailability of propranolol was 104.1 +/- 38.3% after the combined propranolol and nimodipine medication, all other pharmacokinetic parameters remained unchanged. The pharmacological effects on the cardiovascular system were negligible after nimodipine alone. The reductions in blood pressure and pulse rate and the prolongations of typical ECG times observed after propranolol monotherapy and after the combination therapy were of similar size and were almost solely attributed to the action of the beta-blocker. The findings of this study indicate that chronic treatment with nimodipine together with propranolol should not be associated with a clinically relevant interaction.

The influence of nimodipine on hemodynamic parameters and peak and trough plasma concentrations of nifedipine chronically administered to elderly hypertensive patients.

Possible drug interactions between the two calcium channel blockers nimodipine and nifedipine were investigated in 12 elderly patients with stable mild to moderate hypertension. Their individually adjusted nifedipine treatment had been unchanged for at least 5 weeks. There was no evidence of significant changes in nifedipine efficacy as seen from blood pressure and heart rate after a 7-day comedication of 30 mg nimodipine t.i.d. as compared with the findings after combined administration of nifedipine and placebo. Nifedipine steady-state trough and peak concentrations were not significantly altered by concomitant nimodipine administration. On the other hand, nifedipine did not affect nimodipine trough and peak concentrations when compared with published data. Differences in clinical chemistry or tolerance between both treatment regimens did not occur or were marginal, respectively. In conclusion, a clinically relevant drug interaction between nifedipine and nimodipine which might be potentially harmful for patients with hypertension was not observed in this study.

The effect of multiple oral dosing of nimodipine on glibenclamide pharmacodynamics and pharmacokinetics in elderly patients with type-2 diabetes mellitus.

Possible interactions between the calcium channel blocker nimodipine and the hypoglycemic sulphonylurea glibenclamide were investigated in patients with type-2 diabetes mellitus. These 11 patients had taken their individually adjusted antidiabetic treatment unchanged for at least 3 months and showed a satisfactory stabilization on their disease. The concomitant administration of nimodipine 30 mg t.i.d. for 6 days did not change glibenclamide pharmacokinetics as compared with the findings after glibenclamide monotherapy. The normalized AUCss,norm were 11.6 (5.0) kg x h x 1(-1) at glibenclamide monotherapy and 12.3 (5.1) kg x h x 1(-1) after combined medication, resulting in an AUC-ratio for glibenclamide of 109 (23%). Mean elimination half-lives were determined as 2.7 (0.9) h after glibenclamide alone and 3.6 (1.9) h after nimodipine comedication. There was no evidence of significant alterations in glibenclamide efficiency as seen from glucose and insulin kinetics after the simultaneous administration of glibenclamide and nimodipine (insulin Cmax, 57.0 (30.8) mU/l after glibenclamide and 64.4 (32.1) mU/l after combined treatment). Nimodipine pharmacokinetics under nimodipine and glibenclamide steady-state conditions were similar to findings in literature: AUCss,norm 0.10 (0.04) microgram x h x 1(-1), Css,max 20.7 (8.3) microgram x 1(-1). Hemodynamics, clinical chemistry and tolerance did not differ during both treatments. Thus, a clinically relevant drug interaction between nimodipine 30 mg t.i.d. and glibenclamide during long-term treatment can be excluded.

Lack of interaction between diazepam and nimodipine during chronic oral administration to healthy elderly subjects.

1. Nimodipine (30 mg three times daily) and diazepam (10 mg once daily), were given orally to 24 elderly healthy subjects in a randomized, non-blinded, threefold-crossover study. Each of the three treatment periods lasted 5 days separated by 2 week washout phases. 2. Plasma concentrations of nimodipine and diazepam were not affected by the combined treatment. 3. No clinically relevant changes in haemodynamics, ECG recordings, clinical chemistry or haematology were observed after all of the three treatments. The overall frequency of side effects was lowest during monotherapy with nimodipine and highest during diazepam monotherapy. 4. In the test of subjective rating of tiredness (VAS) and the Pauli calculation test, diazepam, alone and with nimodipine co-medication, produced an increase in tiredness and a clear reduction in performance and endurance. After nimodipine monotherapy an improvement was observed only in the Pauli test. Using the critical flicker fusion frequency test (CFF) significant decrements in performance were found after diazepam monotherapy only. 5. In summary, there was no evidence that either nimodipine or diazepam affected the pharmacokinetics, safety and tolerance of each other. However, the CNS-effects of diazepam were compensated partially by nimodipine.

Inhibition of acetylcholinesterase by distigmine bromide (Ubretid).

A randomized phase-I study was performed in a clinical setting in 24 healthy young male subjects, aged 20 to 35 years, to investigate the influence of Ubretid on AChE inhibition following oral and i.m. administration in one of three medication schemes: -single oral (10 mg) and i.m. (0.5 mg) medication (randomized crossover), -multiple oral dosing (5 mg on trial days 1, 2, 3, 5, 7, 9, 11 and 13), -multiple oral dosing (5 mg on trial days 5 to 14) with initial i.m. loading doses (0.5 mg i.m. on trial days 1, 2 and 4). The multiple dosing schemes were chosen as they are both frequently used in clinical practice. The results of the AChE inhibition after Ubretid can be summarized as follows: repeated Ubretid administration as used in this trial did not lead to a cumulation of AChE inhibition. Statistical testing (page test) of maximum AChE inhibition on the last medication days gave no indication of an increased AChE inhibition towards the end of treatment. Compared with the i.m. administration, the Ubretid tablet had a bioavailability of 2.2 +/- 1.1% (mean +/- STD).

Safety and tolerance of trospium chloride in the high dose range.

The safety and tolerance of increasing single oral doses of 20, 40, 80, 120, 180, 240 and 360 mg trospium chloride (Spasmo-lyt, CAS 10405-0204) were investigated in 29 healthy male volunteers in a double-blind placebo-controlled study. Blood pressure, heart rate, ECG, pupillary diameter, salivary secretion, and subjective reports of tolerance revealed no essential differences between placebo and trospium chloride in doses up to 120 mg. Starting with single doses of 180 mg, anticholinergic effects were observed with increasing intensity, i.e., dilatation of the pupils, reduction of salivary flow, and increase of heart rate. While the highest administered dose of 360 mg trospium chloride did not cause any relevant changes of vital parameters (blood pressure, pulse, ECG), it was subjectively rated as quite unpleasant. The data show that trospium chloride is well tolerated in single oral doses well above the current therapeutic daily dose of up to 40 mg.

Pharmacokinetics and relative bioavailability of prajmalium bitartrate after single oral dosing.

Pharmacokinetics and relative bioavailability of the marketed prajmalium bitartrate tablet (Neo-Gilurytmal, CAS 2589-47-1) compared to an oral solution were investigated in an open, randomized, single-dose two-fold crossover study in 20 healthy male volunteers. One subject was identified to be a poor metabolizer. In the study population with normal metabolic status the two oral formulations proved to be bioequivalent with regard to the pharmacokinetic parameters Cmax, AUC(0-Tlast), AUC(0-infinity) and Ae(24h). tmax was prolonged after administration of the tablets. The relative bioavailability of prajmalium bitartrate from the tablet amounted to 112%. The poor metabolizer demonstrated in both oral formulations high plasma concentrations, increased AUCs and prolonged terminal half-lives as well as increased renal excretion of prajmalium bitartrate.

Potentiation of the pressor effect of intravenously administered tyramine during moclobemide treatment.

Potentiation of the pressor effect of tyramine (TYR) by intravenous (i.v.) injection during moclobemide treatment was investigated in healthy volunteers and in depressed patients. The TYR sensitivity factor (TSF) is calculated as the ratio between the dose of TYR required to raise systolic blood pressure by 30 mmHg (TYR 30) without drug and that required with drug. After single-dose administration the TYR 30 for 100 mg moclobemide was 1.8 mg, and those for moclobemide 200 and 300 mg 1.6, compared with 3.2 for placebo, giving corresponding TSF values of 1.7, 2.0 and 2.0 respectively. Twenty-four hours after moclobemide intake, only the 300-mg dose yielded a mean TYR 30 value significantly different from placebo. The same doses of moclobemide given 3 times daily for 1 week resulted in a peak TSF of 2.0 with 100 mg, 2.9 with 200 mg and 3.3 with 300 mg (the latter dose being higher than normally recommended for 3 times daily administration). Nevertheless, 24 h after the last 300-mg dose the TSF was 1.2, similar to that of a single dose. In a study of 17 depressed female patients treated with moclobemide 100 mg 3 times daily, no relevant differences were found in TSF values from those of the volunteers. The authors conclude that, because of the short-lasting, reversible and selective MAO-A-inhibiting effect of moclobemide, there is no marked interaction with tyramine given by i.v. injection. No relevant difference was seen between depressed patients and healthy volunteers in the tyramine pressor effect.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pharmacokinetics of theophylline. Repeated single evening administration of Pulmo-Timelets slow-release capsules in comparison with theophylline slow-release tablets]. / Pharmakokinetik von Theophyllin. Wiederholte einmal abendliche Gabe von Pulmo-Timelets Retardkapseln im Vergleich zu einer Theophyllin-Retardtablette.

In an open randomized cross-over study involving a total of 12 healthy male subjects (mean age: 29 years), the pharmacokinetic profile of Pulmo-Timelets was compared with that of a theophylline controlled-release tablet (each administered at a dose of 600 mg theophylline in the controlled-release form) in the steady state after saturation with a single evening application over 4 days. The relative bioavailability of Pulmo-Timelets vis-a-vis the reference preparation referred to the area under the curve (AUC) in the 24-hour dosage interval, revealed a figure of 82%. Here, the reduced AUC manifested in particular in the absence of concentration peaks associated with a tendency towards somewhat higher plasma concentration 24 hours after administration. While the minima of the plasma concentrations were approximately comparable (mean values 24 hours after the last administration 9.3 and 8.2 mg/l for Pulmo-Timelets and reference preparation, respectively, the maximum concentrations after administration of the reference preparation (average 24.4 mg/l) were about 50% higher than after Pulmo-Timelets (16.3 mg/l). In the case of Pulmo-Timelets throughout the whole period, theophylline plasma concentrations were seen that were in very good agreement with the desired therapeutic range, while, in the case of the reference preparation, definitely and significantly higher concentration peaks occurred in the potentially toxic range.

Gated blood pool scintigraphy as a tool for non-invasive measurements of left ventricular function.

Gated Blood Pool Scintigraphy (GBPS), i.e. the noninvasive evaluation of ventricular performance following the administration of radionuclides as intravascular tracers has had a major impact on many aspects of cardiology and has proven its clinical value and reliability in the past years. Today it is an accepted method in clinical practice, permitting the assessment of both global and regional cardiac function. The most important parameters derived from GBPS volume curves for the determination of left ventricular global function are ejection fraction (EF) at rest and under exercise and peak filling rate of the left ventricle at rest. In addition, GBPS permits the assessment of regional left ventricular function by determining regional EF and phase shifts. Echocardiography is no true alternative to GBPS due to frequent problems in quantitative evaluation and unpredictable errors in patients with non-uniform heart geometry or dyskinetic left ventricles. Thus, GBPS is not only useful in a wide variety of clinical settings, but has become an accepted tool in the methodological approach for non-invasive evaluation of new drugs and sequential drug therapy monitoring. This application of GBPS can be particularly recommended for the investigation of two different problems: a) exclusion of adverse drug effects on left ventricular performance in the process of drug safety evaluation, and b) demonstration of hemodynamic effects of new drugs particularly after long-term medication. GBPS provides valuable information as to the type, onset and duration of hemodynamic changes, permitting the determination of regional changes in myocardial function as well as its global evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Function scintigraphy of the heart in patients with heart valve diseases]. / Funktionsszintigraphie des Herzens bei Patienten mit Herzklappenerkrankungen.

In 58 patients suffering from either stenosis or insufficiency of a single heart valve, gated blood pool scintigraphy was performed to determine the ejection fraction as well as the peak filling and peak ejection rates. It could be demonstrated that in patients with valvular disorders the ejection fraction was only moderately decreased, generally remaining in the lower reference range. The peak filling and ejection rates showed no pathologic changes with the exception of patients with aortic regurgitation where these rates were significantly decreased. Thus, the estimation of left ventricular peak filling and ejection rates may permit diagnosis of myocardial impairment in patients with valvular disease even under resting conditions.

Bioavailability of orally administered mesna.

The bioavailability of orally administered sodium 2-mercaptoethane sulfonate (mesna, Uromitexan drink ampoules) was tested in 18 healthy probands and in 5 tumor patients. Following single oral administration of 20 or 40 mg/kg mesna, 52.4% and 52.6%, respectively, of the dose were excreted in the urine as reactive thiol groups, the remainder as mesna disulfide (dimesna), the only metabolite of mesna; after i.v. injection of 20 mg/kg mesna, 48.7% of the dose administered appeared as thiol groups in the urine. Not until after 13.1 h (20 mg/kg p.o.) and 18.5 h (40 mg/kg p.o.), respectively, concentration drops below the minimum concentration of 100 micrograms/ml presumed to be still reliably protective. However, the elimination pattern and the time when the threshold concentration is reached are subject to marked individual variation. After i.v. administration of 20 mg/kg mesna and 9 times oral administration of 20 mg/kg mesna (the first dose concurrently with the i.v. injection, thereafter every 4 h), or 7 times oral administration of 20 mg/kg mesna (the first dose again concurrently with the i.v. injection, thereafter every 5 h), the percentage of the total dose administered appearing as thiol groups in the urine averaged 41.9% and 37.6%, respectively, up to 17 or 18 h after the last dose. Comparison of periods covering the same time of the day showed the total amount excreted to be higher on day 2 than on day 1.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pupillometry, a clinical-pharmacologic model; statement of its strengths and limitations]. / Die Pupillometrie, ein klinisch-pharmakologisches Modell, Aussagekraft und Grenzen.

A new non-invasive clinical pharmacological model, developed at out Institut, is reported. The principle of the model is the photographic determination of the diameter of the pupil before and after administration of drugs active at the pupilr muscle. The area of the pupilla as a parameter of drug effect can be predicted mathematically. With the reported model the area under the area time curve, the pupillar index and the mean myotic or mydriatic time is determined. The area under the curve gives information about the extent of the drug effect. The pupillar index takes the maximum diameter into account and is even more sensitive than the area under the curve, correcting steep and flat profiles of the area time curve. The mean mydriatic or myotic time gives a robust measurement concerning the duration of the drug effect. To prove the relevance of our model we used treptilamine hydrochloride in four different formulations orally and intravenously. The results show: 1. The model is appropriate to show the effect of drugs on the smooth pupillar muscle concerning rate and extent; 2. The drug treptilamine hydrochloride does change the diameter of the pupils; 3. The drug is active after oral application.

[Pupillometry, a clinical pharmacological model / Relevance and limits (author's transl)]. / Die Pupillometrie, ein klinische-pharmakologisches Modell. Aussagekraft und Grenzen.

A new non-invasive clinical pharmacological model, developed at the Institut für Klinische Pharmakologie, Bobenheim (FR Germany), is reported. The principle of the model is the photographic determination of the diameter of the pupilla before and after administration of drugs active at the pupillar muscle. The area of the pupilla as a parameter of drug effect can be proceeded mathematically. With the reported model the area under the time curve, the pupillary index and the mean myotic or mydriatic time is determined. The area under the curve gives information about the extent of the drug effect. The pupillary index takes the maximum diameter into account and is even more sensitive than the area under the curve, correcting steep and flat profiles of the time curve. The mean mydriatic or myotic time gives a robust measurement concerning the duration of the drug effect. To prove the relevance of our model we used N,N-diethyl-N-(2-[alpha-(tricyclo(2.2.1.02.6)hept-3-ylidene)-benzyloxy]-ethyl)- amine hydrochloride (treptilamine hydrochloride, Asta S 5521) in four different dosages orally and intravenously. The results show: 1. The model is appropriate to show the effect of drugs on the smooth pupillary muscle concerning rate and extent. 2. The drug treptilamine hydrochloride does change the diameter of the pupils. 3. The drug is active after oral application.