STUDIES WITH 4-14C-LYNESTRENOL IN NORMAL AND LACTATING WOMEN

1969 ◽  
Vol 61 (2) ◽  
pp. 255-274 ◽  
Author(s):  
H. J. van der Molen ◽  
P. G. Hart ◽  
H. G. Wijmenga
Keyword(s):  
Oral Administration ◽  
Intravenous Injection ◽  
Breast Feeding ◽  
Oral Contraceptives ◽  
Clearance Rate ◽  
Half Life ◽  
Gelatin Capsule ◽  
Pure Compound ◽  
Lactating Women ◽  
Pharmaceutical Form

ABSTRACT 4-14C-Lynestrenol** was administered either orally or by intravenous injection to women using Lyndiol®*** (5 mg lynestrenol + 150 μg mestranol). In order to study the effect of the pharmaceutical form in oral administration, the radioactive progestagen was given either as the pure compound in the form of a gelatin capsule or as a tablet containing all the ingredients usually present in Lyndiol®-tablets. The concentration of radioactivity in the blood and the excretion of radioactivity in the urine and milk of lactating women were then studied. The clearance rate of radioactivity from the blood was very low. A half-life in the order of 40 h was estimated for labelled »lynestrenol and metabolites«. Within 4–5 days after oral administration of a 14C-lynestrenol containing tablet, 54–65 % of the radioactivity was excreted in the urine, whereas much smaller amounts (in the order of 15 % of the administered dose) were excreted following oral administration of 14C-lynestrenol taken in a capsule. After intravenous administration 45–56 % of the administered radioactivity was recovered in the urine excreted within 4 days after injection. After oral administration of a 14C-lynestrenol containing tablet to 3 lactating women 0.022. 0.028 and 0.088 per cent of the administered radioactivity was excreted in the milk collected during the first 5 days after administration. The results indicate that resorption may be considerably influenced by the pharmaceutical form of the orally administered compound. For oral administration of 5 mg lynestrenol daily, as a Lyndiol®-tablet, it was calculated that in the order of 1 μg (0.02 % of the administered dose) of lynestrenol or its metabolites might be excreted per 100 ml of milk. These data are discussed with regard to the amount of steroids that might be transferred to infants during breast feeding when the mothers take oral contraceptives.

STUDIES WITH 4-14-C-MESTRANOL IN LACTATING WOMEN

1969 ◽  
Vol 61 (4) ◽  
pp. 665-677 ◽  
Author(s):  
H. G. Wijmenga ◽  
H. J. van der Molen
Keyword(s):  
Oral Administration ◽  
Breast Feeding ◽  
Clearance Rate ◽  
Lactation Period ◽  
Lactating Women ◽  
Fourth Patient ◽  
Collection Period

ABSTRACT 14C-Mestranol (5 μc) was administered orally in a Lyndiol®**-tablet (= 5 mg lynestrenol*** + 150 μg mestranol) to four women using Lyndiol® during the lactation period shortly after delivery. The concentration of radioactivity in the plasma and the excretion of radioactivity in the urine and milk were studied. The clearance rate of radioactivity from the blood was very low. A halflife in the order of 40–60 h was found for labelled »mestranol and its metabolites«. In three cases 31–36% of the radioactivity was excreted into the urine within 5 days after oral administration of the labelled material; in the fourth patient this value was about 52 %. During a collection period of 4 days after the oral administration of the 14C-mestranol-containing tablet, 0.0002–0.013 per cent of the administered dose was excreted into the milk. These very low values were partly due to the low amounts of milk that could be collected. It was calculated that with the regular oral administration of one Lyndiol®-tablet daily, with 150 μg mestranol per tablet, about 0.03–0.06 μg (0.02–0.04 % of the administered dose) of mestranol or its metabolites might be excreted per 100 ml milk. The significance of these amounts, in view of the transfer to infants during breast-feeding, is discussed.

scholarly journals Erythropoietin kinetics in rats: generation and clearance

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 646-649 ◽  
Author(s):  
SE Steinberg ◽  
JF Garcia ◽  
GR Matzke ◽  
J Mladenovic
Keyword(s):  
Intravenous Injection ◽  
Plasma Volume ◽  
Rat Model ◽  
Clearance Rate ◽  
Half Life ◽  
Plasma Clearance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Two Compartment Model ◽  
Disappearance Curve

Abstract Detailed studies to analyze the early events of erythropoietin (Ep) secretion and clearance were performed in a rat model using a double antibody radioimmunoassay. Ep clearance was determined following intravenous injection of 1 mL of Ep-rich plasma, 1,080 mU/mL, obtained from phlebotomized rats. Analysis revealed a disappearance curve that conformed to a two-compartment model with an alpha half-life t1/2 of 3.6 minutes and a beta t1/2 of 86 minutes. The volume of distribution was similar to the calculated plasma volume. In anephric animals, there was no change in the plasma clearance rate or the volume of distribution. Rapid Ep secretion was elicited by a single 15 mL/kg phlebotomy (hematocrit decrement 45% to 30%), so that levels reached 20 to 30 times baseline (524 +/- 76 v 24 +/- 7 mU/mL) at five hours, whereas they plateaued for at least 33 hours. The increase in the rate of secretion was geometric, from 9.9 mU/h baseline secretion to 429 mU/h. These data identify a very sensitive and rapidly responsive system for Ep modulation in the rat.

scholarly journals Erythropoietin kinetics in rats: generation and clearance

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 646-649
Author(s):  
SE Steinberg ◽  
JF Garcia ◽  
GR Matzke ◽  
J Mladenovic
Keyword(s):  
Intravenous Injection ◽  
Plasma Volume ◽  
Rat Model ◽  
Clearance Rate ◽  
Half Life ◽  
Plasma Clearance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Two Compartment Model ◽  
Disappearance Curve

Detailed studies to analyze the early events of erythropoietin (Ep) secretion and clearance were performed in a rat model using a double antibody radioimmunoassay. Ep clearance was determined following intravenous injection of 1 mL of Ep-rich plasma, 1,080 mU/mL, obtained from phlebotomized rats. Analysis revealed a disappearance curve that conformed to a two-compartment model with an alpha half-life t1/2 of 3.6 minutes and a beta t1/2 of 86 minutes. The volume of distribution was similar to the calculated plasma volume. In anephric animals, there was no change in the plasma clearance rate or the volume of distribution. Rapid Ep secretion was elicited by a single 15 mL/kg phlebotomy (hematocrit decrement 45% to 30%), so that levels reached 20 to 30 times baseline (524 +/- 76 v 24 +/- 7 mU/mL) at five hours, whereas they plateaued for at least 33 hours. The increase in the rate of secretion was geometric, from 9.9 mU/h baseline secretion to 429 mU/h. These data identify a very sensitive and rapidly responsive system for Ep modulation in the rat.

Turnover of Human Extrinsic (Tissue-Type) Plasminogen Activator in Rabbits

1981 ◽  
Vol 46 (03) ◽  
pp. 658-661 ◽  
Author(s):  
C Korninger ◽  
J M Stassen ◽  
D Collen
Keyword(s):  
Plasminogen Activator ◽  
Intravenous Injection ◽  
Active Site ◽  
Half Life ◽  
Degradation Products ◽  
Gel Filtration ◽  
Tissue Type ◽  
Organ Distribution ◽  
Small Rise

SummaryThe turnover of highly purified human extrinsic plasminogen activator (EPA) (one- and two-chain form) was studied in rabbits. Following intravenous injection, EPA-activity declined rapidly. The disappearance rate of EPA from the plasma could adequately be described by a single exponential term with a t ½ of approximately 2 min for both the one-chain and two-chain forms of EPA.The clearance and organ distribution of EPA was studied by using 125I-labeled preparations. Following intravenous injection of 125I-1abeled EPA the radioactivity disappeared rapidly from the plasma also with a t ½ of approximately 2 min down to a level of 15 to 20 percent, followed by a small rise of blood radioactivity. Gel filtration of serial samples revealed that the secondary increase of the radioactivity was due to the reappearance of radioactive breakdown products in the blood. Measurement of the organ distribution of 125I at different time intervals revealed that EPA was rapidly accumulated in the liver, followed by a release of degradation products in the blood.Experimental hepatectomy markedly prolonged the half-life of EPA in the blood. Blocking the active site histidine of EPA had no effect on the half-life of EPA in blood nor on the gel filtration patterns of 125I in serial plasma samples.It is concluded that human EPA is rapidly removed from the blood of rabbits by clearance and degradation in the liver. Recognition by the liver does not require a functional active site in the enzyme. Neutralization in plasma by protease inhibitors does not represent a significant pathway of EPA inactivation in vivo.

35. The half-life of cobalt in lamb plasma following oral administration of a cobalt supplement

2021 ◽  
Vol 12 (1) ◽  
pp. 25
Author(s):  
J.P. Hanrahan ◽  
D.V. Hession ◽  
N.R. Kendall ◽  
T.W.J. Keady
Keyword(s):  
Oral Administration ◽  
Half Life

Comparative metabolic clearance rate, volume of distribution and plasma half-life of human β-lipotropin and acth

Life Sciences ◽  
1978 ◽  
Vol 23 (23) ◽  
pp. 2323-2330 ◽  
Author(s):  
Anthony S. Liotta ◽  
Choh Hao Li ◽  
George C. Schussler ◽  
Dorothy T. Krieger
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Half Life

Harmful Chemicals and Drugs in Breast Milk

1981 ◽  
Vol 2 (9) ◽  
pp. 279-283
Author(s):  
David S. Smith
Keyword(s):  
Breast Milk ◽  
Anticancer Drugs ◽  
Breast Feeding ◽  
Family Physicians ◽  
Antithyroid Drugs ◽  
Lactating Women ◽  
Antiinfective Agents ◽  
Alternative Drugs

The pediatrician should be aware of the fact that nearly all drugs used in the therapy of lactating women may be found in varying amounts in breast milk. Mothers who must take antithyroid drugs, chloramphenicol, lithium, methadone, most anticancer drugs, radioactive pharmaceuticals and antiinfective agents such as the tetracyclines and metronidazole should not nurse their infants while receiving therapy. It has been our experience that in most instances safer alternative drugs may be selected after discussions with obstetricians, family physicians, and internists. The use of other drugs merits a certain degree of caution; nursing the infant before a dose is given may help to minimize exposure to the infant. Interruption of breast-feeding should be infrequent.

Transfer of Drugs and Other Chemicals Into Human Milk

PEDIATRICS ◽  
1989 ◽  
Vol 84 (5) ◽  
pp. 924-936
Author(s):  
Keyword(s):  
Drug Therapy ◽  
Human Milk ◽  
Breast Feeding ◽  
Drug Exposure ◽  
Chemical Agent ◽  
Blood Concentrations ◽  
Lactating Women ◽  
Chemical Agents ◽  
New Information ◽  
Oral Analgesia

Since the first publication of this statement, much new information has been published concerning the transfer of drugs and chemicals into human milk. This information, in addition to other research published before 1983, makes a revision of the previous statement necessary. In this revision, lists of the pharmacologic or chemical agents transferred into human milk and their possible effects on the infant or on lactation, if known, are provided (Tables 1 to 7). The fact that a pharmacologic or chemical agent does not appear in the Tables is not meant to imply that it is not transferred into human milk or that it does not have an effect on the infant but indicates that there are no reports in the literature. These tables should assist the physician in counseling a nursing mother regarding breast-feeding when the mother has a condition for which a drug is medically indicated. The following questions should be considered when prescribing drug therapy to lactating women. (1) Is the drug therapy really necessary? Consultation between the pediatrician and the mother's physician can be most useful. (2) Use the safest drug; for example, acetaminophen rather than aspirin for oral analgesia. (3) If there is a possibility that a drug may present a risk to the infant (eg, phenytoin, phenobarbital), consideration should be given to measurement of blood concentrations in the nursing infant. (4) Drug exposure to the nursing infant may be minimized by having the mother take the medication just after completing a breast-feeding and/or just before the infant has his or her lengthy sleep periods.

Basis for the ICRP’s updated biokinetic model for systemic astatnie

2022 ◽  
Author(s):  
Richard Wayne Leggett ◽  
Caleigh Samuels
Keyword(s):  
Salivary Glands ◽  
Intravenous Injection ◽  
Half Life ◽  
Particle Therapy ◽  
Radiation Hazard ◽  
Radiation Doses ◽  
Tissue Dose ◽  
Biokinetic Model ◽  
Dose Coefficients ◽  
Icrp Publication

Abstract The ICRP recently updated its biokinetic models for workers in a series of reports called the OIR (Occupational Intakes of Radionuclides) series. A new biokinetic model for astatine, the heaviest member of the halogen family, was adopted in OIR Part 5 (ICRP Publication 151, in press). This paper provides an overview of available biokinetic data for astatine; describes the basis for the ICRP’s updated model for astatine; and tabulates dose coefficients for intravenous injection of each of the two longest lived and most important astatine isotopes, 211At and 210At. Astatine-211 (T1/2 = 7.214 h) is a promising radionuclide for use in targeted α-particle therapy due to several favorable properties including its half-life and the absence of progeny that could deliver significant radiation doses outside the region of α-particle therapy. Astatine-210 (T1/2 = 8.1 h) is an impurity generated in the production of 211At in a cyclotron and represents a potential radiation hazard via its long-lived progeny 210Po (T1/2 = 138 d). Tissue dose coefficients for injected 210At and 211At based on the updated model are shown to differ considerably from values based on the ICRP’s previous model for astatine, particularly for the thyroid, stomach wall, salivary glands, lungs, spleen, and kidneys.

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.

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