AbstractPopulation analysis of pharmacokinetic data for five differing dosage forms and routes for dexamethasone and betamethasone in 48 healthy nonpregnant Indian women was performed that accounted for a partial and complex cross-over design. Single doses of 6 mg dexamethasone phosphate (DEX-P), betamethasone phosphate (BET-P), or 1:1 mixture of betamethasone phosphate and acetate (BET-PA) were administered orally (PO) or intramuscularly (IM). Plasma concentrations collected for two periods over 96 h were described with a two-compartment model with differing PO and IM first-order absorption inputs. Clearances and volumes were divided by the IM bioavailability $${F}_{IM}$$
F
IM
. The homogeneous ages, body weights, and ethnicity of the women obviated covariate analysis. Parameter estimates were obtained by the Laplace estimation method implemented in NONMEM 7.4. Typical values for dexamethasone were clearance ($${CL/F}_{IM})$$
C
L
/
F
IM
)
of 9.29 L/h, steady-state volume ($${{V}_{ss}/F}_{IM})$$
V
ss
/
F
IM
)
of 56.4 L, IM absorption constant $$\left({k}_{aIM}\right)$$
k
aIM
of 0.460 1/h and oral absorption constant ($${k}_{aPO})$$
k
aPO
)
of 0.936 1/h. Betamethasone parameters were CL/FIM of 5.95 L/h, $${Vss/F}_{IM}$$
V
s
s
/
F
IM
of 72.4 L, $${k}_{aIM}$$
k
aIM
of 0.971 1/h, and $${k}_{aPO}$$
k
aPO
of 1.21 1/h. The PO to IM F values were close to 1.0 for both drugs. The terminal half-lives averaged about 7.5 h for DEX, 17 h for BET, and 78 h for BET from BET-PA with the latter reflecting very slow release of BET from the acetate ester. Overall, BET exhibited slower clearance, larger volume of distribution, faster absorption, and longer persistence than DEX. These data may be useful in considering exposures when substituting one form of corticosteroid for another.
New Colistin Population Pharmacokinetic Data in Critically Ill Patients Suggesting an Alternative Loading Dose Rationale
