The Simulation of the Relevance of Absorption Rate Constant and Elimination Rate Constant to the Plasma Drug Concentration

2012 ◽  
Author(s):  
Lei Zhao ◽  
Xinling Shi ◽  
Junhua Zhang
Keyword(s):  
Rate Constant ◽  
Drug Concentration ◽  
Absorption Rate ◽  
Elimination Rate ◽  
Plasma Drug Concentration ◽  
Elimination Rate Constant ◽  
Absorption Rate Constant ◽  
Plasma Drug

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.

Semiparametric approach to pharmacokinetic-pharmacodynamic data

1989 ◽  
Vol 256 (4) ◽  
pp. R1005-R1010
Author(s):  
D. Verotta ◽  
S. L. Beal ◽  
L. B. Sheiner
Keyword(s):  
Steady State ◽  
Rate Constant ◽  
Drug Concentration ◽  
Venous Blood ◽  
Time Lag ◽  
Elimination Rate ◽  
Hysteresis Loops ◽  
Real Data ◽  
Elimination Rate Constant ◽  
Arterial Blood

A semiparametric model for analysis of pharmacokinetic (PK) and pharmacodynamic (PD) data arising from non-steady-state experiments is presented. The model describes time lag between drug concentration in a sampling compartment, e.g., venous blood (Cv), and drug effect (E). If drug concentration at the effect site (Ce) equilibrates with arterial blood concentration (Ca) slower than with Cv, a non-steady-state experiment yields E vs. Cv data describing a counterclockwise hysteresis loop. If Ce equilibrates with Ca faster than with Cv, clockwise hysteresis is observed. To model hysteresis, a parametric model is proposed linking (unobserved) Ca to Cv with elimination rate constant kappa ov and also linking Ca to Ce with elimination rate constant kappa oe. When kappa oe is greater than (or less than) kappa ov clockwise (or counterclockwise) hysteresis occurs. Given kappa oe and kappa ov, numerical (constrained) deconvolution is used to obtain the disposition function of the arterial compartment (Ha), and convolution is used to calculate Ce given Ha. The values of kappa oe and kappa ov are chosen to collapse the hysteresis loops to single curves representing the Ce-E (steady-state) concentration-response curve. Simulations, and an application to real data, are reported.

Prediction of Plasma Drug Concentration Profiles and Pharmacokinetic Parameters of Nifedipine Commercial Tablets using the Convolution Method

2021 ◽  
pp. 5380-5384
Author(s):  
Hamzah Maswadeh ◽  
Ahmed A. H. Abdellatif ◽  
A. Amin Mohammed ◽  
Aiman Y. Alwadi ◽  
A. Ibrahim Mohamed
Keyword(s):  
Drug Concentration ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Concentration Profiles ◽  
Plasma Drug ◽  
First Order ◽  
Convolution Method

The aim of this study was to predict the blood/plasma drug concentration profiles for five brand of nifedipine present on the Saudi Arabia market by using the numerical convolution method and to estimate the pharmacokinetic parameters (Cmax, Tmax, Ka, K and Vd) by the application of the residual method to the predicted plasma drug concentration profiles. Results showed that the higher Cmax was 118.95ng/ml for brand A2 and the lower Cmax was 72.29ng/ml for brand A3. The Tmax was ranged from 2.3 hr to 4.9 hr for brands A2 and A3 respectively. The total area under plasma drug concentration curve (AUCinf.) was in lower value equal to 585.59 ng x hr/ml for brand A2 and the higher value was for brand A5 equal to 743.52ng x hr/ml. The volume of distribution was also increased from 52.5 L for free nifidipine to 72 L for brand A1. The predicted first order elimination rate constant was decreased from 0.34 hr-1 for free nifedipine to 0.17 hr-1 for brand A3. The half-life of nifedapine was increased from 2 hours for free drug to 3.93 hours for brand A3. From this study it can be concluded that brands present in the market that shows similarity in accordance to the Dissimilarity factor f1 are not always guaranty that they will be bioequivalent in vivo and vice versa. Also, this study indicates that the method of convolution is a useful tool for prediction of bioequivalence of different brands present on the market.

scholarly journals Preparation and Pharmacokinetic Study of Daidzein Long-Circulating Liposomes

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Qiao Wang ◽  
Wenjin Liu ◽  
Junjun Wang ◽  
Hong Liu ◽  
Yong Chen
Keyword(s):  
Single Dose ◽  
Drug Concentration ◽  
Drug Loading ◽  
Plasma Drug Concentration ◽  
The Body ◽  
Molar Ratio ◽  
Terminal Phase ◽  
Plasma Drug ◽  
Ultrasonic Time ◽  
Time Required

Abstract In this study, daidzein long-circulating liposomes (DLCL) were prepared using the ultrasonication and lipid film-hydration method. The optimized preparation conditions by the orthogonal design was as follows: 55 to 40 for the molar ratio of soybean phosphatidylcholine (SPC) to cholesterol, 1 to 10 for the mass ratio of daidzein to total lipid (SPC and cholesterol) (w:w), the indicated concentration of 5% DSPE-mPEG2000 (w:w), 50 °C for the hydration temperature, and 24 min for the ultrasonic time. Under these conditions, the encapsulation efficiency and drug loading of DLCL were 85.3 ± 3.6% and 8.2 ± 1.4%, respectively. The complete release times of DLCL in the medium of pH 1.2 and pH 6.9 increased by four- and twofold of that of free drugs, respectively. After rats were orally administered, a single dose of daidzein (30 mg/kg) and DLCL (containing equal dose of daidzein), respectively, and the MRT0−t (mean residence time, which is the time required for the elimination of 63.2% of drug in the body), t1/2 (the elimination half-life, which is the time required to halve the plasma drug concentration of the terminal phase), and AUC0−t (the area under the plasma drug concentration-time curve, which represents the total absorption after a single dose and reflects the drug absorption degree) of daidzein in DLCL group, increased by 1.6-, 1.8- and 2.5-fold as compared with those in the free group daidzein. Our results indicated that DLCL could not only reduce the first-pass effect of daidzein to promote its oral absorption, but also prolong its mean resident time to achieve the slow-release effect.

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.

Cefamandole Distribution in Serum, Adipose Tissue, and Wound Drainage in Morbidly Obese Patients

1986 ◽  
Vol 20 (11) ◽  
pp. 869-873 ◽  
Author(s):  
Henry J. Mann ◽  
Henry Buchwald
Keyword(s):  
Adipose Tissue ◽  
Rate Constant ◽  
Subcutaneous Adipose Tissue ◽  
Elimination Rate ◽  
Elimination Rate Constant ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Tissue Concentrations ◽  
Wound Drainage ◽  
Subcutaneous Adipose

Distribution and elimination of cefamandole 2 g iv were studied in 11 morbidly obese patients during a gastric bypass operation and again on the first postoperative day. Serum, subcutaneous adipose tissue, wound drainage, and urine were analyzed by high performance liquid chromatography for cefamandole and pharmacokinetic parameters from the intraoperative period were compared to those obtained postoperatively. Total body clearance was significantly greater (p < 0.001) postoperatively (297 ml/min) than intraoperatively (254 ml/min). Volume changes were unpredictable but the elimination rate constant tended to increase postoperatively. Renal clearance and percentage of urinary recovery were significantly increased (p < 0.01) postoperatively. The patients had a mean (± SD) volume of the central compartment of 10.3 (± 2.3) L, volume at steady state of 18.3 (± 3.9) L, and elimination rate constant of 1.67 (± 0.63) h−1. Tissue concentrations of cefamandole were highest during the first hour after drug administration and were < 1 μg/g after 3.5 hours. Mean wound drainage concentrations ranged between 10 and 12 μg/ml during a dosing interval and dropped to 7 μg/ml 12 hours after the last dose. Intraoperative dosing of cefamandole is required to maintain subcutaneous adipose tissue concentrations > 1 μg/g during procedures longer than three hours in morbidly obese patients. A postoperative dose of cefamandole 2 g iv q6h will provide sustained and therapeutic concentrations in the wound drainage of morbidly obese patients.

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