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Table 2 Parameter estimates of the final acetazolamide population model in patients with chronic obstructive pulmonary disease (N = 68)a

From: Population pharmacodynamic model of bicarbonate response to acetazolamide in mechanically ventilated chronic obstructive pulmonary disease patients

Parameter

Estimate (%rse)

BSV (%rse) [shrinkage]

Half-life, day

0.25 (fixed)

NA

Bicar0, mmol/L

35.5 (2)

0.101 (9) [0.04]

   × SAPS II effect (SAPS II/50)-0.11

-0.112 (39)

 

   × Corticosteroid effect, if present

1.092 (41)

 

   × Serum chloride effect (chloride/100) -1.17

-1.18 (17)

 

kout, mmol/day

0.395 (17)

0.792 (15) [0.27]

Fur50

187 (21)

 

A50

117 (18)

NA

Residual variability

0.04 (8)

NA

  1. a%rse, percentage relative standard error; ACET, acetazolamide; A50, ACET dosage that provokes 50% of putative maximal effect on serum bicarbonate; BSV, between-subject variability; Bicar0, bicarbonate baseline level; Fur50: furosemide dose that induces a 50% decrease of kout; kout, first-order constant rate of bicarbonate elimination; NA, not applicable; SAPS II, Simplified Acute Physiology Score II; TV: typical value. When COPD patients received ACET, the effect of covariates on observed serum bicarbonate levels was Bicar0 = TV(Bicar0) × (SAPS II/50)-0.11 × (chloride/100)-1.17 × (1.1 if glucocorticoids) and kout = TV(kout) × [1 - furosemide dosage/(furosemide dosage + Fur50)]. Shrinkage was calculated as [1 - sd(η)/ω], where sd(η) and ω are the standard deviation of individual η parameters and the population model estimate of the BSV, respectively.