Daily Intravenous Administration Research Articles

Disposition of Posatirelin. (2). The Transfer into the Fetus and Milk after Single Intravenous Dosing, and the Plasma Level, Distribution and Excretion of Radioactivity after Repeated Intravenous Administration of Posatirelin in Rats.

The transfer of radioactivity into the fetus and milk was studied in pregnant and lactating rats, respectively, after a single intravenous administration of [14C]posatirelin. The plasma level, tissue distribution and excretion of radioactivity were investigated in male rats after 21 consecutive daily intravenous administration of [14C]posatirelin at a dose of 20 mg/kg/day. 1. The fetal concentrations of radioactivity reached the maximum level at 1 hr after dosing, which was about 15% of the maternal plasma concentrations. The fetal concentrations of radioactivity at 48 hr after dosing were about 6 % of the levels in fetus at 1 hr after administration. 2. The levels of radioactivity in the milk reached ap proximately 4.6 μg eq./ml at 1 hr after administration, decreased thereafter with the half life of 5.8 hr. After 6 hr, the milk levels were 3-6 times higher than the corresponding plasma levels. 3. The plasma levels of the radioactivity at 5 min after every dosing were at virtually plateau level of 53-78 μg eq./ml. Those at 24 hr after every dosing increased gradually until 6 days, and reached the plateau level of 0.20-0.34 μg eq./ml thereafter. The plasma levels after the final dosing decreased biphasically with the half lives of about 17 min (α-phase) and about 46 hr (β-phase). The AUC(0-∞) after the final dosing was about 54 μg eq.·hr/ml, which was not of statistically significant different from that after single administration. 4. Among the tissues and organs studied, the kidney showed the highest level of radioactivity at 5 min after repeated administration. In most tissues, the radioactivities were eliminated rapidly until 24 hr after administration but thereafter, the radioactivities decreased slowly. 5. During the period of repeated administration, the ex cretion of the radioactivity in the urine, feces and expired air were of almost constant values of 72-80%, 10-11% and 9-12%, respectively.

Four cases of selenium deficiency in postoperative long-term enteral nutrition

Because selenium is seldom added to formulations for enteral nutrition (EN), postoperative patients who are supported with EN are at risk for selenium deficiency. This report describes four cases of suspected selenium deficiency in long-term EN. Two patients underwent pancreaticoduodenectomy, one underwent total gastro-pancreatectomy, and one underwent esophageal resection and reconstruction with jejunal autotransplantation. They all developed malabsorption syndrome within 2 yr after operation. Enteral nutritional support with an elemental diet was provided continuously for 7–11 yr. Over the past 1–2 yr they experienced increasing bilateral muscular pain and weakness in the legs, gait disturbance, palpitation, and shortness of breath. Investigation for possible trace element deficiency revealed very low levels of selenium in the blood. After 10–20 d of supplementation with daily intravenous administration of selenious acid 0.16 mg/d (100 μg/d of selenium), their blood levels of selenium rose and their symptoms resolved. They were then continued on a maintenance regimen of oral sodium selenite 0.13 mg/d (60 μg/d of selenium).

Glucagon Produced by Recombinant DNA Technology: Repeated Dose Toxicity Studies, Intravenous Administration to CD Rats and Beagle Dogs for Four Weeks

The toxicity of glucagon produced by recombinant DNA technology (Glucagon (ge)) was studied by daily intravenous administration to rats and dogs for 4 weeks. Pancreatic glucagon of bovine or porcine origin (Glucagon Novo) was used as a reference control in the dogs. Glucagon (ge) has the same sequence of the 29 amino acids as pancreatic glucagon of humans, cows, pigs, rats and dogs. The dosages were 0 (control), 0.2, 1.0 and 5.0 mg Glucagon (ge)/kg/day in the rats, and 0 (control), 1.0 and 5.0 mg Glucagon (ge) and 5.0 mg Glucagon (Novo)/kg/day in the dogs. The studies complied with current EEC, US and Japanese guidelines for 4 week toxicity studies of drugs. All dose levels were well tolerated. The plasma glucose and cardiovascular responses to dosing were monitored in the dogs and found to be in agreement with well-known effects of pancreatic glucagon. The most consistent finding in both species was an increase in liver weight. This change was without concomitant pathological deviations in the other parameters examined. There were no differences in the reaction of dogs following treatment with Glucagon (ge) or Glucagon (Novo). A dose of 1 mg Glucagon (ge)/kg/day was regarded as a clear no-toxic-effect-level in both species.

Enhancement by cyclosporin a of metastasis from hamster cheek pouch carcinoma

Daily intravenous administration of 50 mg/kg cyclosporin A (CsA), after excision of cheek pouch tumours induced with 9,10-dimethyl-1,2-benzanthracene (DMBA), enhanced the incidence of cervical lymph node metastasis to 93%, a significant increase over the rates observed for animals receiving a dosage of 25 mg/kg (43%), and for control animals receiving no CsA (40%). No significant effect was evident on the growth rates of the metastasized tumour cells in the lymph node.

Liposomal Encapsulation of Azidothymidine Results in Decreased Hematopoietic Toxicity and Enhanced Activity Against Murine Acquired Immunodeficiency Syndrome

This study has determined the effect of liposomal encapsulation on the hematopoietic toxicity and antiviral activity of 3'-azido-3'-deoxythymidine (AZT) in mice. Daily intravenous administration in the dose range 0.4 to 10 mg/kg body weight for 5 days significantly depressed bone marrow cellularity with a corresponding decrease in red blood cell, blood neutrophil, and monocyte numbers. Maximum toxicity was seen at 2 mg/kg or greater. Liposomal encapsulation of AZT and administration at 2 mg/kg abrogated the toxicity of AZT. The neutrophil inflammatory response to thioglycollate injected intraperitoneally was significantly inhibited by AZT at all doses, whereas liposomal AZT was without effect. The inhibitory activity of AZT against Concanavalin A (Con A)-stimulated splenic lymphocyte proliferation in vitro was reduced on liposomal encapsulation of AZT, while treatment of mice with liposomal AZT but not free AZT resulted in a significant reduction of Con A-stimulated proliferation. Liposomal AZT was more effective than AZT in preventing the development of plasma reverse transcriptase activity and the depletion of Thy 1.2(+)-L3T4+ T cells after infection of mice with LP-BM5 retrovirus. These results indicate that AZT-induced hematopoietic toxicity may not be a limiting factor for antiviral therapy, and that the use of liposomes to deliver AZT results in enhanced antiretroviral activity in mice.

Liposomal encapsulation of azidothymidine results in decreased hematopoietic toxicity and enhanced activity against murine acquired immunodeficiency syndrome

This study has determined the effect of liposomal encapsulation on the hematopoietic toxicity and antiviral activity of 3′-azido-3′- deoxythymidine (AZT) in mice. Daily intravenous administration in the dose range 0.4 to 10 mg/kg body weight for 5 days significantly depressed bone marrow cellularity with a corresponding decrease in red blood cell, blood neutrophil, and monocyte numbers. Maximum toxicity was seen at 2 mg/kg or greater. Liposomal encapsulation of AZT and administration at 2 mg/kg abrogated the toxicity of AZT. The neutrophil inflammatory response to thioglycollate injected intraperitoneally was significantly inhibited by AZT at all doses, whereas liposomal AZT was without effect. The inhibitory activity of AZT against Concanavalin A (Con A)-stimulated splenic lymphocyte proliferation in vitro was reduced on liposomal encapsulation of AZT, while treatment of mice with liposomal AZT but not free AZT resulted in a significant reduction of Con A-stimulated proliferation. Liposomal AZT was more effective than AZT in preventing the development of plasma reverse transcriptase activity and the depletion of Thy 1.2(+)-L3T4+ T cells after infection of mice with LP-BM5 retrovirus. These results indicate that AZT-induced hematopoietic toxicity may not be a limiting factor for antiviral therapy, and that the use of liposomes to deliver AZT results in enhanced antiretroviral activity in mice.

Successful treatment of therapy-resistant acral psoriatic lesions with intravenous administration of Lipo PGE1 (prostaglandin E1 incorporated into lipid microspheres)

Remarkable improvement in psoriatic lesions involving the fingers and nails in three Japanese patients was produced by daily intravenous administration of Lipo PGE1. The lesions in other skin areas did not seem to respond well to this treatment.

Plasma and urine biochemical changes in cats with experimental immune complex glomerulonephritis

Biochemical changes in plasma and urine were monitored in six cats before and during the induction of immune complex-mediated glomerulonephritis (ICGN) by daily intravenous administration of human serum albumin (HSA). The earliest indication of renal dysfunction in the cats was hypoalbuminaemia, which occurred as early as 13 weeks before cats developed clinical signs of renal disease. Proteinuria occurred 2 to 3 weeks before clinical disease, but was sensitive in predicting renal pathology in two cats that did not develop clinical signs of disease. In addition, increased activities of several urinary enzymes were detected in affected cats, with measurement of N-acetyl-beta-D-glucosaminidase and gamma-glutamyl transferase providing the earliest and most sensitive indication of renal damage. These plasma and urine measurements correlated more closely with the renal pathology, observed at postmortem, than clinical assessment of disease. It was concluded that ICGN in the cat could be diagnosed earliest by measurement of plasma protein concentration, whilst disease progress could be effectively monitored by including assays to measure urine protein and urine enzymes.

Antitumor Effect of Recombinant Human Interleukin‐1β Alone and in Combination with Natural Human Tumor Necrosis Factor‐α

In order to investigate the antitumor effect of recombinant human interleukin‐1β (IL‐1β) alone and in combination with natural human tumor necrosis factor‐α (nHuTNF‐α), we used female BDF1 mice bearing Lewis lung carcinoma (3LL). IL‐1β showed an antiproliferative effect against pulmonary metastatic tumors of 3LL in a dose‐dependent manner. We observed 19.6 ± 6.6, 18.6 ± 5.3, 14.1 ± 4.4 and 13.0 ± 6.0 metastatic tumors at doses of 0.5, 1.0, 2.5 and 5.0 μg IL‐1β/mouse/day by daily intravenous administration (the number of metastatic tumors of the control group was 26.3 ± 8.2). Similar results were obtained by intraperitoneal administration, but in this case, mice showed a marked decrease of body weight. When IL‐1β was administered in combination with nHuTNF‐α, pulmonary metastatic tumors decreased much more than when IL‐1β was administered alone. When the control group had 18.6 ± 12.7 metastatic tumors, the nHuTNF‐α group had 12.3 ± 3.9 and the IL‐1β group had 12.8 ± 8.0, the group which was administered both cytokines had a significantly decreased number of 5.6 ± 3.3 metastatic tumors. This antiproliferative effect of IL‐1β in combination with nHuTNF‐α was reduced by the intravenous administration of anti‐asialo GM1 antibody and carrageenan. The number of metastatic tumors was increased from 8.9 ± 8.0 to 18.8 ± 11.4 by anti‐asialo GM1 antibody and from 9.5 ± 6.8 to 28.0 ± 12.3 by carrageenan. It was suggested that asialo GM1‐positive cells and macrophage were two of the most important effectors of the antiproliferative effect of IL‐1β and TNF‐α.

Successful treatment with liposomal amphotericin B in two patients with persisting fungemia

Two granulocytopenic patients in whom fungemia persisted despite therapy with deoxycholate amphotericin B were subsequently successfully treated by daily intravenous administration of amphotericin B entrapped in sonicated liposomes made of egg yolk lecithin, cholesterol and stearylamine in a molar ratio of 4:3:1. High serum concentrations of amphotericin B could be maintained in both patients during therapy with liposomal amphotericin B and were associated with high in vitro antifungal activity. Liposomal amphotericin B was tolerated much better than the deoxycholate preparation. These findings suggest that the liposomal amphotericin B preparation is superior in the treatment of fungemia in granulocytopenic patients, and that randomized trials are warranted.

The Role of Polymorphonuclear Leukocytes in Rat Chronic Serum Sickness‐type Nephritis

In order to investigate the role of polymorphonuclear leukocytes (PMN) in the distribution of antigen in various organs and in the development of nephritis, chronic serum sickness-type nephritis was induced in both anti-rat PMN rabbit serum (APS)-treated and normal rabbit serum (NRS)-treated rats by preimmunization with bovine serum albumin (BSA) and subsequent daily intravenous administration of BSA for 4 weeks. Kinetic studies using radiolabeled BSA showed that accumulation of BSA after the first intravenous administration was reduced by APS treatment in the liver, lungs and spleen and increased in the circulation, but was not affected in the kidneys and glomeruli. Histological studies supported the above findings. After 4 weeks of BSA administration, the BSA accumulation in the kidneys and glomeruli was significantly less in APS-treated rats than in NRS-treated ones, while amounts of BSA in the circulation and other organs were not different between the two groups. Furthermore, APS treatment reduced proteinuria, PMN infiltration and IC deposition in the glomeruli. These observations indicate that PMN play a partial role in IC deposition in the glomerular capillary walls and subsequent destruction of glomerular permeability in chronic serum sickness-type nephritis.

Sudden onset of proteinuria in chronic serum sickness in rats.

1. Daily intravenous administration of bovine serum albumin (BSA) to rats produces chronic serum sickness glomerulonephritis, an immune-complex-mediated renal disease that is eventually always fatal. We have performed a detailed study of the onset of proteinuria in chronic serum sickness in order to assess the long-term consequences of discontinuing daily BSA injections precisely at that very early and well-defined stage of disease. 2. Urine and plasma samples from rats receiving daily BSA injections were collected and analysed daily before the onset of proteinuria, at which time the rats were divided into three groups. Group 1 continued to receive daily BSA injections, in group 2 injections were stopped on the first, and in group 3 on the third, day of proteinuria. Proteinuria began suddenly and was not preceded either by microalbuminuria or abnormalities of plasma composition. The sudden expression of proteinuria was accompanied by an equally rapid development of hypoalbuminaemia and hypercholesterolaemia. Development of the characteristic glomerular histopathology of serum sickness coincided with, but did not precede, the onset of proteinuria. Despite the discontinuation of antigen injections at the onset of proteinuria, basement membrane thickening was evident 8 weeks later; proteinuria persisted and hypercholesterolaemia increased. 3. In this model of immune complex glomerulonephritis, changes in kidney function and immunopathology were abrupt and closely linked, precluding the use of those criteria to predict when proteinuria would begin. Furthermore, extremely brief periods of active immunological injury to the peripheral capillary wall were sufficient to produce persistent abnormalities of glomerular structure and function.

Tumor necrosis factor alpha and interleukin-1 stimulate bone resorption in vivo as measured by urinary [3H]tetracycline excretion from prelabeled mice.

Tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) have been shown to stimulate bone resorption in vitro. We have now investigated whether these cytokines also cause a similar action when administered in vivo. This was made possible by the adaptation of a newly developed technique that enables the continual assessment of bone resorption in vivo in mice by measuring urinary excretion of 3H from [3H]tetracycline-prelabeled animals. Experiments using maneuvers known to influence bone resorption, such as a change in dietary calcium or administration of parathyroid hormone or dichloromethylenebisphosphonate, indicate that the technique is reliable and sensitive in mice. Daily intravenous administration of either recombinant human or recombinant murine TNF-alpha, as well as subcutaneous administration of recombinant human IL-1 alpha, were found to stimulate bone resorption in a dose-dependent manner. The effect was maximal within 2 days. Thus, exogenous TNF-alpha and IL-1 alpha can stimulate bone resorption in vivo, suggesting that these cytokines may also exert a systemic effect on bone.

Pharmacokinetics of idarubicin after daily intravenous administration in leukemic patients

We have studied the plasma pharmacokinetics of idarubicin (4-demethoxydaunorubicin) in eight leukemia patients receiving five daily i.v. injections (7–9 Mg/M 2 per day) of this new anthracycline. For unchanged idarubicin, similar pharmacokinetic parameters were exhibited after the 1st and the 5th injection. Idarubicinol (13-dihydroidarubicin) was identified as the only detectable metabolite of idarubicin in plasma. Due to a protracted half-life (40 h) this compound progressively accumulated in plasma without the occurrence of peaks after the injections. This administration schedule provides therefore an interesting method of dose fractionation of a new anthracycline.

Effect of daily injections of growth hormone-releasing factor and thyrotropin-releasing hormone on growth and endocrine parameters in chickens

The control of growth is a complex mechanism regulated by several metabolic hormones including growth hormone (GH) and thyroid hormones. In avian species, as well as in mammals, GH secretion is regulated by hypothalamic hypophysiotropic hormones. Since thyrotropin-releasing hormone (TRH) and growth hormone-releasing factor (GRF) are potent GH secretagogues in poultry, we were interested in determining the influence of daily intravenous administration of either peptide or both simultaneously on circulating GH and IGF-I concentrations and whether an improvement in growth rate or efficiency would be obtained. Male broiler chicks were injected once daily for a period of 21 days with either GRF (10 μg/kg), TRH (1 μg/kg) or both GRF and TRH (10 and 1 μg/kg respectively) between four and seven weeks of age. On the last day of the experiment, following intravenous injection of TRH, GRF or a combination of GRF and TRH, plasma GH levels were significantly (P<.05) increased to a similar extent in control chicks and in those which had received daily peptide injections for the previous 21 days. Circulating GH levels between 10 and 90 min post-injection were significantly (P<.05) greater and more than additive than GH levels in chicks injected with both GRF and TRH when compared to those injected with either peptide alone. Mean plasma T 3 concentrations during that same time period were significantly elevated (P<.05) above saline-injected control chick levels in birds treated with TRH or GRF and TRH respectively, regardless of whether the chicks had received peptide injections for the previous 21 days. There was no evidence of pituitary refractoriness to chronic administration of either TRH or GRF injection in terms of growth or thyroid hormone secretion. Despite the large elevation in GH concentration each day, growth rate, feed efficiency and circulating IGF-I concentrations were not enhanced. Thus the quantity or secretory pattern of GH secretion induced by TRH or GRF administration was not sufficient to increase plasma IGF-I concentration or growth.

Fetal cardiovascular and catecholamine responses to hypoxemia after chemical sympathectomy.

Chemical sympathectomy was performed in fetal lambs in utero by daily intravenous administration of 6-hydroxydopamine (6HD) until a total dose of 60-70 mg/kg was reached. The completeness of adrenergic denervation was confirmed by the absence of any cardiovascular response to tryamine infusion. Baseline plasma catecholamine concentrations in normoxemic, sympathectomized fetuses were slightly higher than controls but the differences were not statistically significant. The concentration of norepinephrine (NE) was 313 +/- 73 pg/ml after 6HD administration compared with 259 +/- 25 pg/ml in control animals. Similarly, the concentration of epinephrine (E) was 39 +/- 15 pg/ml (6HD) versus 21 +/- 4 pg/ml (control). These mildly elevated catecholamine levels were accompanied by a small but significant increase in resting blood pressure (BP) (P less than 0.05). Heart rate (HR), however, was no different from control. Hypoxemia induced a marked increase in plasma catecholamines in control animals (NE, 2416 +/- 419 pg/ml and E, 2017 +/- 749 pg/ml) along with hypertension and bradycardia. Sympathectomized fetuses maintained a profound NE response to hypoxemia (NE, 1550 +/- 261 pg/ml) but a significant reduction in peak E response was observed (E, 244 +/- 42 pg/ml, P less than 0.05). HR and BP responses to hypoxemia were generally similar to control animals though there appeared to be a brief 1-3 min lag period between the nadir of the bradycardia and the peak of the BP response. We conclude that the generalized chemical sympathectomy after 6HD administration in the fetal lamb in utero is useful in evaluating the interaction of the autonomic nervous system and adrenal medullary function on the regulation of the fetal cardiovascular system.

Innervation of the rat urinary bladder. II. Effects of prostaglandins on the denervated detrusor muscle after bilateral pelvic ganglionectomy

The effects of prostaglandin (PG) F2 alpha and E2 on the denervated smooth muscle of the urinary bladder in female rats were studied in vivo by histochemistry and electron microscopy. The urinary bladder denervated by bilateral removal of the pelvic ganglion was markedly distended, being filled with urine. Daily intravenous administration of PGF2 alpha or PGE2 for 6 days following the operation showed that rats receiving PGE2 urinated remarkably more than those receiving PGF2 alpha. But the ultrastructural changes on the smooth muscle cells, such as dilated tubules of rough endoplasmic reticulum and large Golgi vacuoles, were more prominent in the PGF2 alpha administrated urinary bladders than in PGE2 administrated ones. On occasion, cholinergic ganglion cells happened to be encountered in the muscular layer of a rat urinary bladder. These intramural ganglion cells and the cholinergic nerve fibers surrounding the cells displayed strong acetylcholinesterase activity, unaffected by bilateral pelvic ganglionectomy.

Endotoxin-induced fever and associated haematological and blood biochemical changes in the goat: the effect of repeated administration and the influence of flurbiprofen

Flurbiprofen, a potent non-steroidal anti-inflammatory and antipyretic agent, was given as an intravenous infusion (2 mg/kg) followed by a bolus injection of 1 mg/kg six hours later. After drug administration body temperature and rumen contractions were slightly depressed, whereas urea values gradually increased; serum sorbitol dehydrogenase (SDH) activity, plasma iron concentration and the number of circulating lymphocytes were significantly lower. Intravenous injection of endotoxin from Escherichia coli O111B4 (0.1 microgram/kg) caused shivering, fever, inhibition of rumen contractions, changes in heart rate, lymphopenia, neutropenia followed by neutrophylic leucocytosis, changes in urea values, hypoferraemia, hypozincaemia and a decline in serum alkaline phosphatase (ALP) activity, whereas gamma-glutamyltranspeptidase, glutamic oxalacetic transaminase, lactic dehydrogenase and SDH values were not significantly altered. Pretreatment with flurbiprofen completely abolished the febrile reactions to endotoxin. The endotoxin-induced inhibition of rumen contractions was only delayed. The drug blocked the initial tachycardia to endotoxin but did not prevent the secondary biphasic increase in heart rate. Flurbiprofen failed to modify the endotoxin-induced decrease in both plasma zinc and serum ALP activity whereas the decline in plasma iron concentration was delayed. After drug pretreatment the changes in circulating white blood cells were more pronounced. These data demonstrate that most of the haematological, blood biochemical and clinical effects of endotoxin cannot be blocked by flurbiprofen, and that these effects are not due to the increase in body temperature alone. Tolerance induced by repetitive daily intravenous administration of endotoxin resulted in an almost complete abolition of all the effects. However, the plasma iron values from tolerant goats were significantly lower than those from non-tolerant animals, which demonstrates that the development of a refractory state can result in modification of this biochemical parameter.

A phase I clinical trial of aclacinomycin A administered on a five-consecutive-day schedule.

In the Phase I study, the new anthracycline aclacinomycin A was given to 22 advanced cancer patients on a schedule of daily intravenous administration for five days repeated every four weeks. The limiting toxicity was myelosuppression, which was severe at a dose of 30 mg/m2 per day for five days. Platelet nadirs were more marked than those of white cells and occurred at day 21. Some patients had moderate nausea and vomiting. No hepatic or renal toxicity was observed, and alopecia was minimal. Cardiac function was monitored prospectively, using radionuclide left ventricular ejection fractions and serial ECGs. One patient developed transient atrial fibrillation; and one other, who had previously received 380 mg/m2 doxorubicin, developed congestive heart failure. Otherwise there was no evidence of cardiac toxicity. No tumor regressions were seen. We conclude that 1509 mg/m2 given in five daily 30 mg/m2 fractions is a maximum tolerated dose of aclacinomycin A. This is higher than the reported MTD of 120 mg/m2 for single bolus injection. We recommend a Phase II starting dose of 25 mg/m2 per day for good-risk patients and 20 mg/m2 per day for poor-risk patients when the drug is given on this schedule.

Evaluation of a nonisotopic technique for studies of in vivo cholesterol metabolism in mini-pigs using inhibition of 7-dehydrocholesterol reductase by AY 9944.

The feasability of a nonisotopic method for assessing the approximate rates of sterol fluxes and its regulations was studied within the plasma pool of intact animals. Appropriate daily intravenous administration of AY 9944 leads to a constant, incomplete inhibition in the enzymatic conversion from 7-dehydrocholesterol. Thereby a unique intermediate in cholesterol synthesis such as 7-dehydrocholesterol can be accumulated in the plasma. The established intermediate pool of 7-dehydrocholesterol in the plasma represents, under certain conditions, an indicator pool for the cholesterol pool in the animal. Our data show that the metabolic behaviour of the accumulated 7-dehydrocholesterol during the administration of AY 9944 is not different from cholesterol and that 7-dehydrocholesterol does not induce a feed-back inhibition in overall sterol synthesis. The rate of appearance of the endogenous sterol tracer 7-dehydrocholesterol and its removal from the plasma pool create a constant plasma 7-dehydrocholesterol level during chronic AY 9944 administration and under steady state conditions during the experimental period. The values determined for the artificially built-up intermediate pool of 7-dehydrocholesterol in the plasma are a relative measure for the complex process of the cholesterol metabolism in the animal. Manipulations in cholesterol metabolism with its resulting alterations in the “input” or “output” of sterols in the rapid exchangeable plasma pool lead to changes in the intermediated (tracer) 7-dehydrocholesterol plasma pool.