PMID- 7593736
OWN - NLM
STAT- MEDLINE
DCOM- 19951212
LR  - 20240109
IS  - 0271-0749 (Print)
IS  - 0271-0749 (Linking)
VI  - 15
IP  - 4 Suppl 2
DP  - 1995 Aug
TI  - Moclobemide: relationships between dose, drug concentration in plasma, and 
      occurrence of adverse events.
PG  - 84S-94S
AB  - The relationship between exposure to moclobemide and the occurrence of adverse 
      events (AEs) was quantified by applying a population approach to data collected 
      during phase III/IV studies. A total of 965 measurements of moclobemide 
      concentration in plasma were available from 357 depressed patients included in a 
      series of clinical studies; 539 AEs were reported by the 236 patients with at 
      least one concentration measurement > or = 400 micrograms/liter. Using relatively 
      few blood samples per patient (mean, 2.7), the average concentration in plasma on 
      the day an AE was observed was calculated (CAE,pred) from population kinetic 
      parameter estimates. The frequency of AEs, normalized by exposure time in months 
      (AEs/Mo), was grouped according to dose and concentration categories and examined 
      in relation to age, gender, adverse event severity, and concomitant medication. 
      CAE,pred was more powerful than the observed concentration or daily dose in 
      detecting relationships between exposure to moclobemide and the occurrence of 
      AEs. There was a relationship between CAE,pred and AEs/Mo, with 0.58 events at 
      concentrations between 1,000 and 1,999 micrograms/liter and 2.78 events at 
      concentrations of 4,000 micrograms/liter and above. Within each concentration 
      category, the number of AEs decreased with increasing severity. Advancing age was 
      not associated with an increase of AEs/Mo. AEs were more frequent in females than 
      in males in all treatment intensity categories (ratio, 1.4). There was no 
      indication of supra-additive effects by concomitant medication, including all 
      drugs used in the study population. This investigation demonstrates the 
      successful use of observational data from clinical studies in the assessment of 
      quantitative relationships between drug exposure and the occurrence of AEs.
FAU - Guentert, T W
AU  - Guentert TW
AD  - F. Hoffmann-La Roche Ltd., Basel, Switzerland.
FAU - Banken, L
AU  - Banken L
FAU - Hilton, S
AU  - Hilton S
FAU - Holford, N H
AU  - Holford NH
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Clin Psychopharmacol
JT  - Journal of clinical psychopharmacology
JID - 8109496
RN  - 0 (Antidepressive Agents)
RN  - 0 (Benzamides)
RN  - PJ0Y7AZB63 (Moclobemide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antidepressive Agents/*adverse effects/*pharmacokinetics/therapeutic use
MH  - Benzamides/*adverse effects/*pharmacokinetics/therapeutic use
MH  - Depressive Disorder/*complications/*metabolism/psychology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Moclobemide
MH  - Patient Compliance
MH  - Product Surveillance, Postmarketing
EDAT- 1995/08/01 00:00
MHDA- 1995/08/01 00:01
CRDT- 1995/08/01 00:00
PHST- 1995/08/01 00:00 [pubmed]
PHST- 1995/08/01 00:01 [medline]
PHST- 1995/08/01 00:00 [entrez]
AID - 10.1097/00004714-199508001-00014 [doi]
PST - ppublish
SO  - J Clin Psychopharmacol. 1995 Aug;15(4 Suppl 2):84S-94S. doi: 
      10.1097/00004714-199508001-00014.