Area-Based Estimation of the Initial Volume of Distribution and Elimination Rate Constant following Intravenous Bolus Injection

1991 ◽  
Vol 80 (11) ◽  
pp. 1042-1050
Author(s):  
Soo Peang Khor ◽  
Stephen L. Johnson ◽  
Michael Mayersohn
Keyword(s):  
Rate Constant ◽  
Bolus Injection ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Elimination Rate Constant ◽  
Intravenous Bolus ◽  
Intravenous Bolus Injection ◽  
Initial Volume

Theophylline Disposition following Parenteral Feeding of Malnourished Patients

1993 ◽  
Vol 27 (7-8) ◽  
pp. 846-851
Author(s):  
Paul G. Cuddy ◽  
John F. Bealer ◽  
Elizabeth L. Lyman ◽  
L. Beatty Pemberton
Keyword(s):  
Parenteral Nutrition ◽  
Rate Constant ◽  
Tertiary Care ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Elimination Rate Constant ◽  
Parenteral Feeding ◽  
Maximum Plasma ◽  
Serum Theophylline ◽  
Theophylline Disposition

OBJECTIVE: To investigate the effect of parenteral nutrition on theophylline disposition in malnourished patients. DESIGN: Before-after trial. SETTING: Tertiary care center. PATIENTS: Ten patients with historic, anthropometric, and laboratory evidence of malnutrition. INTERVENTIONS: Patients received two 5-mg/kg intravenous infusions of theophylline separated by at least 48 hours of glucose-based parenteral nutrition providing the entire estimated nutritional requirements. MAIN OUTCOME MEASURES: Following each theophylline administration, serum theophylline samples were collected over a 24-hour period for delineation of maximum plasma concentrations, volume of distribution, elimination rate constant, clearance, and area under the curve. RESULTS: Peak plasma theophylline concentrations were significantly lower prior to feeding (5.3 μmol/L, 95 percent confidence interval [CI] 0.78–10.0 μmol/L, p=0.028). Volume of distribution decreased after parenteral feeding (0.08 L/kg, 95 percent CI 0.006–0.15 L/kg, p=0.037). The elimination rate of theophylline increased after parenteral feeding reflected by an increase in the elimination rate constant (0.06 h1, 95 percent CI 0.01–0.10 h−1, p=0.023). CONCLUSIONS: This study suggests that parenteral nutrition using a glucose-based solution acutely influences theophylline disposition in malnourished patients.

Pharmacological properties of YM-254890, a specific Gαq/11 inhibitor, on thrombosis and neointima formation in mice

2005 ◽  
Vol 94 (07) ◽  
pp. 184-192 ◽  
Author(s):  
Masatoshi Taniguchi ◽  
Yumiko Moritani ◽  
Toshio Uemura ◽  
Takeshi Shigenaga ◽  
Hajime Takamatsu ◽  
...  
Keyword(s):  
Oral Administration ◽  
Vascular Injury ◽  
Bolus Injection ◽  
Thrombus Formation ◽  
Therapeutic Window ◽  
Pharmacological Properties ◽  
Neointima Formation ◽  
Intravenous Bolus ◽  
Test Drug ◽  
Intravenous Bolus Injection

SummaryThe pharmacological properties of YM-254890,a specific Gαq/11 inhibitor, on acute thrombosis and chronic neointima formation after vascular injury have been investigated. FeCl3 was used to induce vascular injury in the carotid artery of mice. For the thrombosis studies, the test drug was either intravenously or orally administered before vascular injury. For the neointima studies, the test drug was orally administered 1 h before and twice daily for 1 week after vascular injury. Histological analysis was then performed 3 weeks later. YM-254890 significantly inhibited ex vivo platelet aggregation 5 min after intravenous bolus injection at 0.03 mg/kg or more, and 1 h after oral administration at 1 mg/kg. YM-254890 significantly inhibited thrombus formation after intravenous bolus injection at 0.03 mg/kg as well as after oral administration at 1 mg/kg, but tail transection bleeding time was significantly prolonged at 0.1 mg/kg for intravenous injection and 3 mg/kg for oral administration. Furthermore, oral administration of YM-254890 dose-dependently inhibited neointima formation 3 weeks after vascular injury with significant effects at 1 mg/kg twice daily for 1 week. Clopidogrel also significantly inhibited neointima formation at its antithrombotic dose, but its inhibitory potency was less than that of YM-254890. However, YM-254890 significantly reduced systemic blood pressure at doses 3 times higher than those that produced significant inhibitory effects on thrombosis and neointima formation. Though the systemic use of YM-254890 may be limited, owing to its narrow therapeutic window, this unique compound is a useful research tool for investigating the physiological roles of Gαq/11.

In Vivo Utilization of Cystine-Containing Synthetic Short-Chain Peptides after Intravenous Bolus Injection in the Rat

1988 ◽  
Vol 118 (12) ◽  
pp. 1470-1474 ◽  
Author(s):  
Peter Stehle ◽  
Sabine Albers ◽  
Leonhard Pollack ◽  
Peter Fürst
Keyword(s):  
Bolus Injection ◽  
Short Chain ◽  
Intravenous Bolus ◽  
Intravenous Bolus Injection

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.

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.

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.

Sign in / Sign up

Export Citation Format

Share Document