Estimation of Absorption Rate Constant in a One-Compartment Model with the Profile of the Bioavailable Dose Eliminated as a Function of Multiples of Half-Life

1993 ◽  
Vol 82 (12) ◽  
pp. 1298-1300 ◽  
Author(s):  
P. Macheras ◽  
M. Symillides ◽  
C. Reppas
Keyword(s):  
Rate Constant ◽  
Half Life ◽  
Absorption Rate ◽  
Compartment Model ◽  
Absorption Rate Constant

scholarly journals Pharmacokinetics of human chorionic gonadotropin after i.m. administration in goats (Capra hircus)

Reproduction ◽  
2012 ◽  
Vol 144 (1) ◽  
pp. 77-81 ◽  
Author(s):  
M Saleh ◽  
M Shahin ◽  
W Wuttke ◽  
M Gauly ◽  
W Holtz
Keyword(s):  
Rate Constant ◽  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Half Life ◽  
Absorption Rate ◽  
Elimination Rate ◽  
Elimination Rate Constant ◽  
Capra Hircus ◽  
Absorption Rate Constant ◽  
Biological Half Life

The present investigation addresses the pharmacokinetics of human chorionic gonadotropin (hCG), intramuscularly (i.m.) administered to goats. Nine pluriparous does of the Boer goat breed, 2–6 years of age and weighing 45–60 kg, were administered 500 IU hCG (2 ml Chorulon) deep into the thigh musculature 18 h after superovulatory FSH treatment. Blood samples were drawn from the jugular vein at 2 h intervals for the first 24 h, at 6 h intervals until 42 h, and at 12 h intervals until 114 h after administration. After centrifugation, plasma hCG concentrations were determined by electrochemiluminescence immunoassay. Pharmacokinetical parameters were as follows: lag time, 0.4 (s.e.m. 0.1) h; absorption rate constant, 0.34 (s.e.m. 0.002) h; absorption half-life, 2.7 (s.e.m. 0.5) h; elimination rate constant, 0.02 (s.e.m. 0.002) h; biological half-life, 39.4 (s.e.m. 5.1) h; and apparent volume of distribution, 16.9 (s.e.m. 4.3) l. The plasma hCG profile was characterized by an absorption phase of 11.6 (s.e.m. 1.8) h and an elimination phase of 70.0 (s.e.m. 9.8) h, with considerable individual variation in bioavailability and pharmacokinetical parameters. Biological half-life was negatively correlated (P<0.05) with peak concentration (r=−0.76), absorption rate constant (r=−0.78), and elimination rate constant (r=−0.87). The results indicate that after rapid absorption, hCG remains in the circulation for an extended period. This has to be taken into account when assessing the stimulatory response to hCG treatment on an ovarian level.

A New Method for the Estimation of Absorption Rate Constant in Two-Compartment Model by Extravascular Administration

2020 ◽  
Vol 109 (5) ◽  
pp. 1802-1810 ◽  
Author(s):  
Ye Zeng ◽  
Jianxiong Liu ◽  
Wenjie Liu ◽  
Shan Jiang ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Rate Constant ◽  
Absorption Rate ◽  
Compartment Model ◽  
New Method ◽  
Absorption Rate Constant ◽  
Two Compartment Model

scholarly journals Pharmacokinetic-Pharmacodynamic Modeling of Unboosted Atazanavir in a Cohort of Stable HIV-Infected Patients

2012 ◽  
Vol 57 (1) ◽  
pp. 517-523 ◽  
Author(s):  
Sylvain Goutelle ◽  
Thomas Baudry ◽  
Marie-Claude Gagnieu ◽  
André Boibieux ◽  
Jean-Michel Livrozet ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Rate Constant ◽  
Virological Failure ◽  
Absorption Rate ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Pharmacodynamic Modeling ◽  
Absorption Rate Constant ◽  
Time Curve ◽  
The Relationship

ABSTRACTLimited data on the pharmacokinetics and pharmacodynamics (PK/PD) of unboosted atazanavir (uATV) in treatment-experienced patients are available. The aim of this work was to study the PK/PD of unboosted atazanavir in a cohort of HIV-infected patients. Data were available for 58 HIV-infected patients (69 uATV-based regimens). Atazanavir concentrations were analyzed by using a population approach, and the relationship between atazanavir PK and clinical outcome was examined using logistic regression. The final PK model was a linear one-compartment model with a mixture absorption model to account for two subgroups of absorbers. The mean (interindividual variability) of population PK parameters were as follows: clearance, 13.4 liters/h (40.7%), volume of distribution, 71.1 liters (29.7%), and fraction of regular absorbers, 0.49. Seven subjects experienced virological failure after switch to uATV. All of them were identified as low absorbers in the PK modeling. The absorption rate constant (0.38 ± 0.20 versus 0.75 ± 0.28 h−1;P= 0.002) and ATV exposure (area under the concentration-time curve from 0 to 24 h [AUC0–24], 10.3 ± 2.1 versus 22.4 ± 11.2 mg · h · liter−1;P= 0.001) were significantly lower in patients with virological failure than in patients without failure. In the logistic regression analysis, both the absorption rate constant and ATV trough concentration significantly influenced the probability of virological failure. A significant relationship between ATV pharmacokinetics and virological response was observed in a cohort of HIV patients who were administered unboosted atazanavir. This study also suggests that twice-daily administration of uATV may optimize drug therapy.

Absorption Enhancing Effect of Sodium Dodecyl Sulfate on Metformin Hydrochloride in Rat Colon

2013 ◽  
Vol 544 ◽  
pp. 426-430
Author(s):  
Dong Dong Jing ◽  
Yu Liu ◽  
Ruo Yu Liu ◽  
Hua Fan ◽  
Guo Feng Li ◽  
...  
Keyword(s):  
Sodium Dodecyl Sulfate ◽  
Rate Constant ◽  
Absorption Rate ◽  
Sodium Dodecyl ◽  
Rat Colon ◽  
Metformin Hydrochloride ◽  
Loop Model ◽  
Absorption Rate Constant ◽  
Enhancing Effect ◽  
Dodecyl Sulfate

The aim of this study was to observe the absorption enhancing effect of sodium dodecyl sulfate on metformin hydrochloride in colon of rat. Using in vivo intestinal loop model in rat while the ileum was took as blank group and colon as the experiment groups with different concentration of sodium dodecyl sulfate (1%, 2%, 4%). The colon/ileum ratio of the absorption rate constant of metformin hydrochloride was evaluated through calculating the residual dose of circulating solution in presupposition time points. Intergroup absorption rate constant and the rising percent of the absorption rate constant were different significantly (P<0.05). The absorption rate constant of colon were -0.22±0.03, -0.37±0.06, -0.89±0.09, -0.86±0.05μg•h-1•cm-1 (n=6) and the rising percent of the constant absorption value were 68.66 ± 8.28%, 304.88 ± 28.76%, 293.75 ± 33.19% (n=6), respectively. The result showed that the absorption of metformin hydrochloride was increased with the concentration of sodium dodecyl sulfate. However, the absorption rate constant reached maxium when the concentration of sodium dodecyl sulfate was 2%, this may be because the circulating metformin hydrochloride solution could be more viscous which affect the absorption of metformin hydrochloride when sodium dodecyl sulfate was raised. In conclusion, the absorption of metformin hydrochloride can be promoted by sodium dodecyl sulfate in the colon of rat and this can provide biophamaceutics data for novel pharmaceutical preparation.

Serum Concentrations of Salicylic Acid following Topically Applied Salicylate Derivatives

1996 ◽  
Vol 30 (9) ◽  
pp. 935-940 ◽  
Author(s):  
Pina Morra ◽  
William R Bartle ◽  
Scott E Walker ◽  
S Nicole Lee ◽  
Susan K Bowles ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Rate Constant ◽  
Maximum Concentration ◽  
Methyl Salicylate ◽  
Absorption Rate ◽  
The Other ◽  
Pharmacokinetic Parameters ◽  
Absorption Rate Constant ◽  
Serum Concentrations ◽  
Women Volunteers

OBJECTIVE: To compare the rate and extent of systemic salicylate absorption following single and multiple applications of two topically applied analgesics, one containing methyl salicylate and the other containing trolamine salicylate. DESIGN: Two-period, two-treatment, randomized, crossover, multiple-dose study in healthy men and women volunteers. PARTICIPANTS: Six men and six women volunteers, 21–14 years of age. INTERVENTIONS: Subjects applied 5 g of an ointment containing 12.5% methyl salicylate twice daily for 4 days (8 doses) or a cream containing trolamine 10% twice daily for two doses, to a 10-cm2 area on the thigh. Treatment order and leg (right or left) were assigned randomly. Subjects were crossed over to the alternate treatment on the other leg after a minimum washout period of 7 days. MAIN OUTCOME MEASURES: The total amount of salicylate recovered in the urine during two dosing intervals (24 hours) on each study day, relative to the applied dose, was used to calculate the bioavailability of each product. Mean standard pharmacokinetic parameters including area under the curve, maximum concentration (Cmax), time to maximum concentration, and minimum concentrations at steady-state were determined from serum concentrations. Serum concentrations were fit to three pharmacokinetic models and the suitability of each model was evaluated. Estimates of absorption rate constant, clearance, volume, and fraction absorbed on day 1 were estimated by using the best-fitting model. RESULTS: Salicylic acid could not be detected in serum after trolamine application. However, concentrations between 0.31 and 0.91 mg/L were detected within 1 hour of the first application of methyl salicylate and Cmax, between 2 and 6 mg/L were observed following the seventh application on day 4. Both the extent and rate of absorption changed after the first 24 hours. The absorption rate constant increased significantly from the first to the seventh dose (first dose absorption rate constant: 0.16 h−1; seventh dose: 0.28 h−1; p < 0.035). Urinary recovery of total salicylate (salicylic acid and principal metabolites of salicylic acid) during the first 24 hours of the methyl salicylate phase averaged 175.2 mg, exceeding the 6.9 mg (p < 0.05) recovered during the trolamine phase. The recovery of salicylate in the urine in the first 24 hours after application of methyl salicylate was significantly greater than the 1.4% recovered after application of trolamine (p < 0.05). Furthermore, the fraction of methyl salicylate recovered in the urine increased significantly from 15.5% on day 1 to approximately 22% on the second, third, and fourth days. CONCLUSIONS: A considerable amount of salicylic acid may be absorbed through the skin after topical application of methyl salicylate products and this may increase with multiple applications. Caution is warranted in patients for whom systemic salicylate may be hazardous or problematic.

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