Arzneimittel Forsch
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Arzneimittel Forsch · Mar 1997
Randomized Controlled Trial Clinical TrialClinical pharmacokinetics of meloxicam.
Meloxicam (CAS 71125-38-7, UH-AC 62 XX) is a new non-steroidal anti-inflammatory drug (NSAID) which was developed for the treatment of osteoarthritis and rheumatoid arthritis. The basic clinical pharmacokinetics of meloxicam (7.5-30 mg) have been investigated in 78 healthy male volunteers after single and multiple dosing via oral, intravenous and rectal routes. Plasma concentrations of meloxicam were determined by validated high performance liquid chromatography (HPLC) methods. ⋯ Steady state is achieved within 3 to 5 days. In addition, the pharmacokinetic parameters are linear over the entire dose range, there are no changes with multiple dosing and bioequivalence was shown for a number of different formulations. The results indicate that meloxicam is suitable for once-daily administration and that a switch from one formulation to another is easily possible if necessary or convenient for the patient.
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Arzneimittel Forsch · Jan 1997
Comparative StudyStudies on the abstinence-like overshoot following reversal of the potent 19-isoamyl derivative of etorphine with naloxone. A comparison with the opioids fentanyl and alfentanil.
Reversal of opioid-related respiratory depression is often accompanied by an "acute abstinence like syndrome" with hypertension, tachycardia, and pain. This overshoot was used to investigate the extent at which opioids of high potency but different structure are involved in naloxone-induced abstinence. In 10 awake and trained mongrel dogs two highly mu-selective compounds, alfentanil and fentanyl, were given in cumulative doses and at different occasions (30-60-120-240 micrograms/kg, and 6-12-24-48 micrograms/kg, respectively). ⋯ However, no precipitation on an acute abstinence-like syndrome affecting antinociception or inducing cardiovascular overshoot was observed. This may stem from an intense binding and slow dissociation of the ligand from the receptor site or may be due to high binding affinity to both the mu and the kappa receptor site. Opioids which interact with various receptor sites may be of clinical interest for substitution therapy in opioid dependent addicts.
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Arzneimittel Forsch · Dec 1996
Comparative StudyTherapeutic effect of the quinolone prodrug prulifloxacin against experimental urinary tract infections in mice.
The in vitro antibacterial activity of prulifloxacin (CAS 123447-62-1, NM441), a new quinoline prodrug, against clinical isolates from urinary tract infections was investigated. In addition, it was compared with ofloxacin (CAS 82419-36-1), levofloxacin (CAS 100986-85-4), ciprofloxacin urinary tract infections in mice, as well as its pharmacokinetics. 1. The antibacterial activity of NM394 (6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazeto[3,2- a]quinoline-3-carboxylic acid), an active metabolite of prulifloxacin, against gram-positive clinical isolates was inferior to that of levofloxacin and tosufloxacin, and equal to that of ofloxacin and ciprofloxacin. ⋯ The maximal concentration and AUC of prulifloxacin in lung and kidney were slightly higher than the corresponding values for ciprofloxacin but only 1/2 to 1/4 of the values for ofloxacin, levofloxacin and tosufloxacin. In conclusion, prulifloxacin (NM394) showed potent antibacterial activity against clinical isolates and potent therapeutic efficacy against experimental infection in spite of its lower AUCs compared with the reference drugs. These findings suggest that prulifloxacin may be a useful drug in the treatment of urinary tract infections.
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Arzneimittel Forsch · Sep 1996
Studies on the chronic oral toxicity of an analgesic drug combination consisting of acetylsalicylic acid, paracetamol and caffeine in rats including an electron microscopical evaluation of kidneys.
The analgesic drug combination Thomapyrin consisting of acetylsalicylic acid (CAS 50-78-2, ASA), paracetamol (CAS 103-90-2, NAPAP) and caffeine (CAS 58-08-2) in the ratio 5:4:1 was investigated for its chronic toxicity in rats. For comparison the individual drugs ASA and NAPAP as well as the double combination ASA+NAPAP were tested in equipotent doses. 20 male and 20 female rats per group (Chbb:THOM/SPF) received doses of 50, 100 and 200 mg/kg of the combination ASA+NAPAP+caffeine, 45 and 180 mg/kg of the combination ASA+NAPAP, and 50 and 200 mg/kg of the individual drugs ASA or NAPAP over a period of 6 months. The daily dose was splitted into two parts and administered 3 h apart. ⋯ Semi-thin section evaluation and transmission electron microscopy showed only minor changes. Taking all tubular and vascular changes together (total mean), the animals of the NAPAP group were slightly more affected than those of the other groups. Summing up it can be concluded that the nephrotoxic potential of the combination ASA+NAPAP+caffeine, if existing at all, was marginal even after prolonged administration, and that it does not exceed that of the monosubstances when given at pharmacologically equipotent doses and clinically relevant exposures.
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Arzneimittel Forsch · Feb 1996
Comparative Study Clinical Trial[Determination of systolic left ventricular time interval using the doppler technique. Analysis of aortic flow spectrum with transthoracic echocardiography].
In 10 healthy volunteers (age 21-28 years; mean age 24.8 years +/- 1.9 years) systolic left ventricular time intervals (STI) were determined by analysis of aortic Doppler flow pattern. This method was compared with conventional calculation of STI, using electrocardiogram, carotid pulse curve and phonocardiography, which were registered in synchronicity to the Doppler examination. Both, CW- and PW Doppler echocardiography constantly showed slightly lower values than the conventional method. This referred to basic measurements as well as to measurements after the application of isoprenaline and quinidine. The PW Doppler method underestimated the conventional method concerning the electromechanic systole (QS2) by on average 3.98%, the left ventricular ejection period (LVET) by on average 2.24% and the pre-ejection period (PEP) by on average 7.3%. Using CW-Doppler-method, QS2 was on average 5.31% and LVET was on average 6.67% smaller than the values determined by conventional method, whereas PEP was overestimated by on average 1.69%. The study documented that positive and negative inotropic pharmacological effects were measured reliably by the Doppler-echocardiographic method. Isoprenaline caused a significant shortening of frequency corrected QS2 (QS2c) from -55 +/- 17 to -85 +/- 20 ms (p < 0.05) using the PW-Doppler method; frequency corrected PEP (PEPc) was shortened from -40 +/- 14 to -67 +/- 14 ms (p < 0.05). The CW Doppler method also showed a statistically significant reduction of QS2c (from -64 +/- 18 to -89 +/- 25 ms; p < 0.05) and PEPc (from -37 +/- 16 to -64 +/- 12; p < 0.05). Likewise, the conventional method demonstrated statistically significant shortening of QS2c and PEPc after application of isoprenaline. LVETc did not change in a state of positive inotropy, no matter which method was used for determination. The negative inotropic effect of quinidine, measured by PW-Doppler, resulted in a prolongation of QS2c from -55 +/- 16 to -32 +/- 24 ms (p < 0.05) and of LVETc from -20 +/- 11 to +6 +/- 17 ms (p < 0.05). Using CW Doppler method, quinidine led to a lengthening of QS2c from -63 +/- 16 to -42 +/- 22 (p < 0.05) and of LVETc from -33 +/- 11 to -12 +/- 8 ms (p < 0.05). The conventional method also demonstrated a statistically significant increase of QS2c and LVETc. None of the 3 methods in question showed a statistically significant alteration of PEPc in the negative inotropic state. ⋯ Doppler-echocardiographic analysis of aortic flow pattern constitutes a new method for the measuring of systolic time intervals. Basic values as well as changes due to positive or negative inotropic effects are reliably determined, in comparison with conventional methods the measurements are slightly lower.