Minocycline in the treatment of rheumatoid arthritis: relationship of serum concentrations to efficacy.
OBJECTIVE
To assess the relationships between serum concentrations of minocycline and clinical efficacy and toxicity during the treatment of patients with rheumatoid arthritis (RA) with minocycline.


METHODS
Forty patients with active RA were administered minocycline (maximal oral dose 100 mg twice a day) for 26 weeks. At 3 time points during the treatment, serum samples were collected for measurement of minocycline activity using a microbiological assay. An analysis of variance was performed to estimate an extrapolated concentration at time = 0 (C0) for each patient separately and this value of C0 was regarded to be proportional to the average serum concentration in each patient. The relation between C0 and clinical response and between C0 and the occurrence of adverse effects was evaluated.


RESULTS
Minocycline was detected in 96 serum samples from 37 patients. Eighty-two percent of the variance in serum concentrations was accounted for by a model incorporating patient, dose, and time effects. A weak correlation between C0 and clinical response, as expressed by a Ritchie articular index and number of swollen joints, was demonstrated. No correlation was seen between C0 and toxicity, including gastrointestinal or vestibular adverse effects.


CONCLUSIONS
Results suggest a relationship between the serum concentrations of minocycline and the clinical response, including Ritchie articular index and number of swollen joints, in the treatment of patients with RA. No relationship was seen between the serum concentrations of minocycline and its toxicity.
Kloppenburg
M
M
Department of Rheumatology, University Hospital Leiden, The Netherlands.
Mattie
H
H
Douwes
N
N
Dijkmans
B A
BA
Breedveld
F C
FC
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D009994:Osmolar Concentration; D011446:Prospective Studies; D016896:Treatment Outcome
D008911:Minocycline