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Titolo:
RO-48-6791, A SHORT-ACTING BENZODIAZEPINE - PHARMACOKINETICS AND PHARMACODYNAMICS IN YOUNG AND ELDERLY VOLUNTEERS IN COMPARISON WITH MIDAZOLAM
Autore:
HERING W; IHMSEN H; ALBRECHT S; SCHWILDEN H; SCHUTTLER J;
Indirizzi:
UNIV ERLANGEN NURNBERG,ANASTHESIOL KLIN,KRANKENHAUSSTR 12 D-91054 ERLANGEN GERMANY
Titolo Testata:
Anasthesist
fascicolo: 12, volume: 45, anno: 1996,
pagine: 1211 - 1214
SICI:
0003-2417(1996)45:12<1211:RASB-P>2.0.ZU;2-D
Fonte:
ISI
Lingua:
GER
Keywords:
RO 48-6791; MIDAZOLAM; PHARMACOKINETIC-PHARMACODYNAMIC MODELING; CONCENTRATION-EFFECT RELATIONSHIP; RECOVERY TIMES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
5
Recensione:
Indirizzi per estratti:
Citazione:
W. Hering et al., "RO-48-6791, A SHORT-ACTING BENZODIAZEPINE - PHARMACOKINETICS AND PHARMACODYNAMICS IN YOUNG AND ELDERLY VOLUNTEERS IN COMPARISON WITH MIDAZOLAM", Anasthesist, 45(12), 1996, pp. 1211-1214

Abstract

The objectives of the present study were to compare in a randomized double-blind crossover study design the concentration-effect relationships of Ro 48-6791, a new benzodiazepine agonist, and midazolam, following infusion in young and elderly male volunteers. Therefore, linearlyincreasing plasma concentrations were generated by computer controlled infusion pumps to achieve a deep hypnotic effect. The endpoint of the infusion was defined by loss of response to loud verbal commands anda median frequency of the recorded EEG power spectrum below 4 Hz. Arterial blood samples were collected in regular intervals up to 6 hours after cessation of the infusion. The method of pharmacokinetic-pharmacodynamic modeling was used to quantify the concentration-effect relationship, including age related differences, already in this early phaseI study. The total clearance of Ro 48-6791 was found to be 1410+/-380vs. 399+/-91 ml min(-1) for midazolam (mean+/-SD; P<0.005) and the central volume of distribution to be 20.5+/-7.1 vs. 7.9+/-3.01, respectively (P<0.005). The comparison between young and elderly volunteers yielded for Ro 48-6791 a statistically not significant reduction of 16% for clearance with age and a slowed distribution of 47% for midazolam (P<0.05). The recovery period for Ro 48-6791 was reduced by 66% (P<0.005) in the young and 45% (P<0.01) in the elderly, respectively, in comparison with midazolam. With respect to the total doses administered, Ro 48-6791 appeared to be 2.5 times as potent as midazolam in all volunteers (P<0.001). Comparing both age groups, the doses necessary to cause similar effects were reduced by one half for both compounds in theelderly (P<0.001). The major advantages of Ro 48-6791 compared to midazolam were its shorter duration of action as well as the faster recovery and thus the better controllability. Further investigations would have to confirm these results in a greater number of patients. The applied method of pharmacokinetic-pharmacodynamic modeling not only allowed to quantify the efficacy of Ro 48-6791 but also provided data to augment the safety for fur ther investigations.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 12:51:22