An Estimation Method of the Clearance for a One-Compartment Model of a Single Bolus Intravenous Injection by a Single Sampling

2011 ◽  
Vol 22 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Takashi Funatogawa ◽  
Ikuko Funatogawa
Keyword(s):  
Intravenous Injection ◽  
Estimation Method ◽  
Compartment Model ◽  
Single Bolus ◽  
Bolus Intravenous Injection

Pharmacokinetics and Tissue Residues of Sulfathiazole and Sulfamethazine in Pigs

1994 ◽  
Vol 57 (9) ◽  
pp. 796-801 ◽  
Author(s):  
LIEVE S. G. VAN POUCKE ◽  
CARLOS H. VAN PETEGHEM
Keyword(s):  
Intravenous Injection ◽  
Half Life ◽  
Intramuscular Injection ◽  
Compartment Model ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Tissue Concentrations ◽  
Single Intravenous Injection ◽  
The Individual ◽  
Residue Study

The plasma pharmacokinetics and tissue penetration of sulfathiazole (ST) and sulfamethazine (SM) after intravenous and intramuscular injection in pigs were studied. Following a single intravenous dose of 40 mg ST/kg of bodyweight or 80 mg SM/kg of bodyweight, the plasma ST and SM concentrations were best fitted to a two-compartment model. The areas under the curve were 447 ± 39 and 1485 ± 41 mg/h/L, clearances were 0.090 ± 0.007 and 0.054 ± 0.001 L/kg/h, volumes of distribution were 1.16 ± 0.16 and 0.77 ± 0.06 L/kg, half-lifes in distribution phase were l.18 ± 0.57 and 0.23 ± 0.16 h and half-lifes in eliminations phase were 9.0 ± l.6 and 9.8 ± 0.6 h. When the two compounds were administered simultaneously as a single intravenous injection, the pharmacokinetic parameters for ST were not significantly different. The values for SM show statistical differences for some important parameters: α, β and the AUC0–>∞ were significantly decreased and t1/2α, Vd and CIB were significantly increased. It can be concluded that after a single intravenous injection of 40 mg/kg, sulfathiazole has a high tl/2β resulting in higher tissue concentrations. This half-life, which is higher than what is reported in the literature, is not influenced by the simultaneous presence of sulfamethazine. The tl/2β for sulfamethazine after a single intravenous injection of 80 mg/kg is comparable to the data from the literature and is not influenced by the presence of sulfathiazole. Sulfathiazole and SM were also administered simultaneously as an intramuscular injection to healthy pigs at a dosage of 40 and 80 mg/kg bodyweight. Pharmacokinetic experiments were conducted on three pigs. From this pharmacokinetic study it can be concluded that upon a single intramuscular administration of 40 mg/kg of ST and 80 mg/kg of SM the absolute bioavailability in pigs is 0.92 ± 0.04 for ST and l.01 ± 0.07 for SM. Six pigs received five intramuscular im) injections as a single dose of ST and SM every 24 h for five consecutive days for the residue study. The pigs were slaughtered at different times after the last dose was given and samples were taken from various tissues and organs. Concentrations were determined by a microbiological method and a HPTLC method. No edible tissue contained more than 100 μg/kg of the individual sulfonamides after 10 days of withdrawal. It means that adult animals which have a shorter half-life and thus lower tissue concentrations will certainly meet the economic community EC) maximum residue limits after a 10 days withdrawal period.

Bolus Intravenous Injection of Phosphorothioate Oligonucleotides Causes Hypotension by Acting as α1-Adrenergic Receptor Antagonists

1999 ◽  
Vol 160 (3) ◽  
pp. 289-296 ◽  
Author(s):  
Patrick L. Iversen ◽  
Kurtis G. Cornish ◽  
Laurie J. Iversen ◽  
John E. Mata ◽  
David B. Bylund
Keyword(s):  
Intravenous Injection ◽  
Adrenergic Receptor ◽  
Receptor Antagonists ◽  
Bolus Intravenous Injection

The vagus nerve in the thermoregulatory response to systemic inflammation

1997 ◽  
Vol 273 (1) ◽  
pp. R407-R413 ◽  
Author(s):  
A. A. Romanovsky ◽  
C. T. Simons ◽  
M. Szekely ◽  
V. A. Kulchitsky
Keyword(s):  
Intravenous Injection ◽  
Systemic Inflammation ◽  
Second Phase ◽  
Thermoregulatory Response ◽  
Cool Environment ◽  
Bolus Intravenous Injection ◽  
High Doses ◽  
Colonic Temperature ◽  
Dose Dependent ◽  
Higher Doses

Experimentally, systemic inflammation induced by a bolus intravenous injection of lipopolysaccharide (LPS) may be accompanied by three different thermoregulatory responses: monophasic fever (the typical response to low doses of LPS), biphasic fever (medium doses), and hypothermia (high doses). In our recent study [Romanovsky, A. A., V. A. Kulchitsky, C. T. Simons, N. Sugimoto, and M. Szekely. Am. J. Physiol. (Regulatory Integrative Comp. Physiol.). In press], monophasic fever did not occur in subdiaphragmatically vagotomized rats. In the present work, we asked whether vagotomy affects the two other types of thermoregulatory response. Adult Wistar rats were vagotomized (or sham operated) and had an intravenous catheter implanted. On day 28 postvagotomy, the thermal responses to the intravenous injection of Escherichia coli LPS (0, 1, 10, 100, or 1,000 micrograms/kg) were tested in either a neutral (30 degrees C) or slightly cool (25 degrees C) environment. Three major results were obtained. 1) In the sham-operated rats, the 1 microgram/kg dose of LPS caused at 30 degrees C a monophasic fever with a maximal colonic temperature (Tc) rise of approximately 0.6 degree C; this response was abated (no Tc changes) in the vagotomized rats. 2) At 30 degrees C, all responses to higher doses of LPS (10-1,000 micrograms/kg) were represented by biphasic fevers (the higher the dose, the less pronounced the first and the more pronounced the second phase was); none of these biphasic fevers was altered in the vagotomized animals. 3) In response to the 1,000 micrograms/kg dose at 25 degrees C, hypothermia occurred: Tc changed by -0.5 +/- 0.1 degree C (nadir); this hypothermia was exaggerated (-1.1 +/- 0.1 degrees C) in the vagotomized rats. It is concluded that vagal afferentation may be important in the mediation of the response to minor amounts of circulating LPS, whereas the response to larger amounts is brought about mostly (if not exclusively) by nonvagal mechanisms. This difference may be explained by the dose-dependent mechanisms of the processing of exogenous pyrogens. Vagotomized animals also appear to be more sensitive to the hypothermizing action of LPS in a cool environment; the mechanisms of this phenomenon remain speculative.

Allopurinol kinetics in humans as a means to assess liver function: comparison of different models

1987 ◽  
Vol 253 (2) ◽  
pp. R352-R360 ◽  
Author(s):  
G. van Waeg ◽  
T. Groth ◽  
F. Niklasson ◽  
C. H. de Verdier
Keyword(s):  
Liver Function ◽  
Intravenous Injection ◽  
Healthy Subjects ◽  
Tight Binding ◽  
Compartment Model ◽  
Central Compartment ◽  
Fractional Rate ◽  
Computer Based ◽  
Loading Tests ◽  
Three Compartment Model

To describe the mechanisms involved in allopurinol kinetics after intravenous injection in humans, a number of alternative computer-based biodynamic models were designed. Distribution processes were described with two-compartment as well as with three-compartment kinetics for both allopurinol and its metabolite oxipurinol. These two major physiological alternatives were combined with biochemical models assuming either competitive or tight-binding-complex inhibition kinetics. The four resulting basic models were evaluated (and successively improved) using sets of plasma allopurinol and oxipurinol concentration curves, measured after intravenous injection in healthy subjects and in patients with different degrees of liver function. A three-compartment model with tight-binding-complex inhibition was selected and used to analyze the 35 loading tests performed. One of the parameters estimated in this way, the fractional rate constant for transport of allopurinol from the central compartment to the metabolically active (liver) compartment (kA31), turned out to be a powerful discriminative parameter between a group of healthy subjects, a group of patients with slightly to moderately reduced overall liver function, and a group with severely reduced overall liver function [kA31(min-1) = 0.136 +/- 0.042 (mean +/- SD, n = 13), 0.072 +/- 0.024 (n = 13), and 0.025 +/- 0.015 (n = 8), respectively].

scholarly journals Parameter Estimation Method for Compartment Model ---- PET Inspection ----

2019 ◽  
Vol 24 ◽  
pp. 570-573
Author(s):  
Tetsuo Hattori ◽  
Yoshiro Imai ◽  
Koji Kagawa ◽  
Yo Horikawa ◽  
Yusuke Kawakami* ◽  
...  
Keyword(s):  
Parameter Estimation ◽  
Estimation Method ◽  
Compartment Model ◽  
Parameter Estimation Method

Pharmacodynamic Properties of Long Lasting Butyryl Heparin Derivatives in the Rabbit

1992 ◽  
Vol 67 (05) ◽  
pp. 550-555 ◽  
Author(s):  
S Saivin ◽  
C Caranobe ◽  
M Petitou ◽  
J C Lormeau ◽  
G Houin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Intravenous Injection ◽  
Low Molecular Weight Heparin ◽  
Subcutaneous Administration ◽  
Constant Infusion ◽  
Daily Injection ◽  
Low Molecular Weight ◽  
Vein Thrombosis ◽  
Bolus Intravenous Injection

SummaryThis paper reports on the pharmacodynamic properties of butyryl derivatives of unfractionated heparin (C4-UH) and of low molecular weight heparin (C4-CY 216) after bolus intravenous injection, constant infusion and subcutaneous administration to rabbits. The pharmacodynamic properties of the two butyryl derivatives were compared to those of the parent compounds, unfractionated heparin (UH) and low molecular weight heparin (CY 216). After bolus intravenous injection of increasing doses, the disposition of the butyryl derivatives were comparable to that of their parent compounds up to 3 mg kg-1. Over this dose, their clearances became 2 to 3 times lower. These long lasting properties were confirmed by constant intravenous infusion experiments. After subcutaneous administration, the bioavailability of C4-UH remained low (10%) at any dose while that of C4-CY 216 ranged from 42 to 120%. If these findings are confirmed in man, these new derivatives open the possibility of treating established deep vein thrombosis with only one daily injection of a butyryl derivative of low molecular weight heparin.

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