Linear pharmacokinetic equations allowing direct calculation of many needed pharmacokinetic parameters from the coefficients and exponents of polyexponential equations which have been fitted to the data

107

Oxycodone chloride (0.07 mg kg-') was given by intravenous bolus to nine young adult surgical patients on the first postoperative day. Plasma was sampled for up to 12 h. Mean values of tyl/,, CL and Vss were 222 min, 0.78 1 min-1 and 2.60 1 kg-1, respectively. The concentrations of the metabolite noroxycodone was also measured. The mean AUC(0,12) ratio of noroxycodone to oxycodone was 0.33. Oxymorphone was not detected.

Section: Assays and Pharmacokinetic Analysismentioning

confidence: 99%

The pharmacokinetics of oxycodone after intravenous injection in adults.

Pöyhiä

Olkkola

Seppαlä

et al. 1991

107

“…The coefficients and exponents of the chosen equation were used for the calculation (Wagner, 1976) Group data were expressed either as median (and range) or as mean ± s.e. mean unless otherwise indicated.…”

Section: Pharmacokinetic and Statistical Analysismentioning

confidence: 99%

Pharmacokinetics of ranitidine in critically ill patients.

Ilett¹,

Nation

Tjokrosetio³

et al. 1986

1 The plasma pharmacokinetics of ranitidine (50 mg i.v.) have been studied in 17 critically ill patients in an intensive care unit. Measurements of gastric aspirate pH were also made in 16 of these patients. Ranitidine therapy was part of the patients' normal drug regimen. 2 Ranitidine plasma concentration was measured by high performance liquid chromatography and appropriate polyexponential equations were fitted to concentration-time data to enable calculation of relevant pharmacokinetic parameters. Values of the volume of the initial dilution space (median = 89 ml kg-') and volume of distribution at steady state (median = 1.541 kg-') were about 60% of corresponding mean literature values for healthy controls. Plasma clearance (median = 4.22 ml min7l kg-1) and terminal half-life (median = 4.7 h) were about 2-3 fold less and 2-3 fold greater, respectively, than values for healthy controls. There was wide interpatient variation in all the pharmacokinetic parameters. Renal impairment was considered to be largely responsible for the low plasma clearance. 3 Gastric aspirate pH was measured at 0, 1 and 7 h after ranitidine administration and 58% of samples were found to be above pH 4. Four patients had gastric pH values which were consistently below pH 4 despite average trough plasma ranitidine concentrations equal to or greater than those required for a 50% suppression of gastric acid secretion in normal volunteers.

“…AUC values were computed using the linear trapezoidal rule and the quotient of the last antipyrine concentration and Xz. Assuming complete oral bioavailability [15], volume of distribution (V ) and clearance (CLO) were computed using standard pharmacokinetic formulae [16]. Urine concentrations of antipyrine and its metabolites were also measured by h.p.l.c.…”

Section: Methodsmentioning

confidence: 99%

Liver blood flow, antipyrine clearance, and antipyrine metabolite formation clearance in patients with chronic active hepatitis and alcoholic cirrhosis.

Bauer

O’Sullivan

Reiss

et al. 1994

1 Duplex scanning was used to measure liver blood flow (hepatic artery and main branches of the portal and hepatic veins) in six healthy subjects, five cirrhotic patients, and six hepatitis patients. Antipyrine clearance and formation clearances to its metabolites were also measured. 2 Compared with healthy control subjects, cirrhotic patients had a lower hepatic vein blood flow (-76%, P < 0.05). This was due primarily to a lower portal vein blood flow (-36%, NS). A statistically significant difference in liver blood flow between patients with hepatitis and normal subjects was not detected. 3 Antipyrine half-life, clearance, and the area under the serum drug concentration vs time curve were significantly different in cirrhotic patients compared with the healthy subjects (mean ± s.d.-healthy controls: t, 2 = 13.7 ± 3.0 h, CL = 30.0 ± 8.6ml h-' kg-', AUC = 549 ± 139 mg 1-1 h; cirrhotic patients: ti,2 = 32.4 ± 1.7 h, CL = 12.3 ± 2.1 ml h-1 kg-', AUC = 1061 ± 218 mg 1-1 h; P < 0.008). Antipyrine halflife, clearance, and the area under the serum drug concentration vs time curve were not significantly different in hepatitis patients compared with the healthy subjects (hepatitis patients: tb = 14.3 ± 3.7 h, CL = 29.3 ± 8.5 ml h-1 kg-I, AUC = 498 ± 142 mg I1-h). The volume of distribution of antipyrine was similar in all three groups of subjects. 4 Formation clearances to 3-OH-methylantipyrine, 4-OH-antipyrine, and norantipyrine were all lower (P < 0.009) in cirrhotic patients compared with normal subjects and hepatitis patients. However, only the formation clearance to norantipyrine was lower (P < 0.002) in hepatitis patients when compared with normals. 5 There were strong correlations between the logarithmic transformations of the formation clearances for all antipyrine metabolites (r = 0.88-0.93, P < 0.0001). However, the only orthogonal regression line with a slope not significantly different from one was that for norantipyrine and 3-OH-methylantipyrine indicating that these two metabolites may be metabolized by a common enzyme(s). 6 Weak correlations were found between the logarithmic transformations of hepatic vein blood flow and antipyrine clearance and the logarithmic transformations of hepatic vein blood flow and formation clearances to antipyrine metabolites (r= 0.54-0.62, P < 0.05). 7 Cirrhotic patients may have difficulty metabolizing drugs with high hepatic extraction ratios or drugs that are eliminated by the same liver enzyme systems which produce the three major metabolites of antipyrine. Hepatitis patients may have difficulty metabolizing drugs that share the same hepatic enzyme system responsible for the formation of norantipyine from antipyrine.