Aims This open, controlled study investigated the effect of concomitant 15
mg oral meloxicam on the pharmacokinetics of lithium in healthy male volunt
eers.
Methods On days 1-14 lithium was coadministered with meloxicam to 16 volunt
eers; on days 10-14 Lithium was administered in individualized dosage regim
es to achieve stable lithium plasma concentrations in the lower therapeutic
range of 0.3-0.7 mmol l(-1). A 12 h steady-state concentration profile for
lithium was obtained at day 14, after which meloxicam was withdrawn. The l
ithium dose remained unchanged from day 15 to day 22, at which time a secon
d Lithium concentration profile was determined.
Results Lithium and meloxicam were well tolerated throughout the study and
all 16 volunteers completed the study. Lithium predose concentrations (C-pr
e,C-ss) and area under the curve (AUC(ss)) values both increased by 21% (pa
ired t-test P = 0.0002; 90% confidence intervals for test/reference ratios:
113-130% and 115-128%, respectively) when lithium was coadministered with
meloxicam compared with values obtained for lithium alone. The geometric me
an lithium C-pre,C-ss was 0.65 mmol l(-1) when coadministered with meloxica
m and 0.54 mmol l(-1) for lithium alone. Lithium C-max,C-ss values were inc
reased by 16% by coadministration of meloxicam, from 0.97 mmol l(-1) to 1.1
2 mmol l(-1). The total plasma clearance of lithium was lower with concomit
ant meloxicam administration (82.5% of value for lithium alone).
Conclusions Meloxicam (15 mg) moderately increased the plasma concentration
of lithium in healthy volunteers, but by a magnitude thought to be of low
clinical relevance. Nevertheless, lithium plasma concentrations should be c
losely monitored in patients receiving concomitant meloxicam and lithium th
erapy.