Pharmacokinetics and tissue localization of doxycycline polyphosphate and doxycycline hydrochloride in the rat

Michel, G.; Mosser, J.; Olle, J.

doi:10.1007/bf03189618

Cited by 15 publications

(17 citation statements)

References 11 publications

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“…Doxycycline is highly lipophilic and would be expected to be distributed widely in the chicken. Nevertheless, the V^m*) of 0.28 ± 0.02 I/kg determined in the present study was much lower than that reported for other species: 0.75 I/kg in adult humans (Raghuram & Krishnaswamy, 1982), 1.38 I/kg in calves (Riond et al, 1989), 1.5 to 3.5 I/kg in dogs (Michel et al, 1979), 2.28 I/kg in cows and ewes (Ziv & Sulman, 1974), 4.5 to 7 I/kg in rats (Michel et al, 1984) and 9.78 I/kg in goats (Jha et al, 1989). The lower value of apparent volume of distribution found in the present study may be attributed to higher plasma protein binding, as well as a lower gut reabsorption of drug in the chicken.…”

Section: Discussioncontrasting

confidence: 71%

“…or oral administration in chickens could be described adequately by a two-compartment open model. Experiments performed in mammals (Ziv & Sulman, 1974;Michel et al, 1984;Jha et al, 1989;Riond et al, 1989) have led to the same conclusion. Disappearance of the drug from the plasma of chickens was characterized by an initial rapid distribution phase followed by a slower elimination phase.…”

Section: Discussionmentioning

confidence: 73%

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Pharmacokinetics of doxycycline in broiler chickens

et al. 1994

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SUMMARYDoxycycline was given to two groups of eight chickens at a dose of 20 mg/kg of body weight, intravenously (i.v.) or orally. Plasma concentration was monitored serially for 12 h after each administration. Another group of 30 chickens was given 20 mg/kg orally every 24 h for 4 days, and plasma and tissue concentrations determined serially after the last administration. Concentrations of doxycycline were measured using high-performance liquid chromatography. Pharmacokinetic variables were calculated, using a two-compartment open model. The elimination half-life and the mean residence time for plasma were 6.03 ± 0.45 and 7.48 ± 0.38 h, respectively, after oral administration and 4.75 ±0.21 and 2.87 ±0.11 h, respectively, after i.v. administration. After single oral administration, doxycycline was absorbed rapidly, with T max of 0.35 ± 0.02 h. Maximum plasma concentration was 54.58 ± 2.44 μ/ml. Oral bioavailability of doxycycline was found to be 41.33 ± 2.02%. Doxycycline was widely distributed in tissues and considerable concentrations were found following oral administration of 20 mg/kg on four successive days. The results indicate that doxycycline concentrations were cleared slowly and were at or below the accepted drug tolerance levels in the marker tissues within 5 days after dosing.

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Section: Discussioncontrasting

confidence: 71%

Section: Discussionmentioning

confidence: 73%

Pharmacokinetics of doxycycline in broiler chickens

et al. 1994

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“…No human PLTP mRNA was detected in brain tissue, probably because doxycycline poorly crosses the blood brain barrier (Michel et al 1984). The distribution pattern of murine PLTP in human PLTP expressing PLTPtg//rtTAtg mice is comparable with the pattern found in C57BL/6 wildtype mice (Jiang and Bruce 1995).…”

Section: Discussionmentioning

confidence: 58%

“…Tre-PLTPtg//rtTAtg Àdox 1.5 ± 1.0 0.0 ± 0.0* 1.5 ± 0.9* 0.9 ± 0.1** 0.9 ± 0.1 0.8 ± 0.1 0.5 ± 0.1 1.0 ± 0.1 * p < 0.001, versus Tre-PLTPtg//rtTAtg + dox * p < 0.001, versus Tre-PLTPtg + dox explained by doxycycline distribution between tissues: after oral doxycycline administration to rats, highest levels were measured in excretory organs (i.e., liver and kidney) (Michel et al 1984). No human PLTP mRNA was detected in brain tissue, probably because doxycycline poorly crosses the blood brain barrier (Michel et al 1984).…”

Section: Discussionmentioning

confidence: 99%

“…Our inducible mouse model shows a broad pattern of human PLTP expression (liver, kidney > lung > spleen, heart, adrenal, adipose tissue). It is not known whether this is a reflection of the normal regulation of PLTP expression found in human tissues (Day et al 1994), a reflection of the doxycycline distribution among tissues (Michel et al 1984), or a combination of both. The high human PLTP expression levels in liver and kidney might be Plasma samples were subjected to electrophoresis on precast 4-15% SDS-polyacrylamide gradient gels and subsequently stained with Coomassie blue Tre-PLTPtg//rtTAtg +dox 1.2 ± 0.5 10.5 ± 2.6 11.7 ± 2.7 1.0 ± 0.3** 1.2 ± 0.5 0.7 ± 0.2 1.0 ± 0.5 1.2 ± 0.4…”

Section: Discussionmentioning

confidence: 99%

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Inducible expression of phospholipid transfer protein (PLTP) in transgenic mice: acute effects of PLTP on lipoprotein metabolism

et al. 2007

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One main determinant in high-density lipoprotein (HDL) metabolism is phospholipid transfer protein (PLTP), a plasma protein that is associated with HDL. In transgenic mice overexpressing human PLTP we found that elevated plasma PLTP levels dose-dependently increased the susceptibility to dietinduced atherosclerosis. This could be mainly due to the fact that most functions of PLTP are potentially atherogenic, such as decreasing plasma HDL levels. To further elucidate the role of PLTP in lipoprotein metabolism and atherosclerosis we generated a novel transgenic mouse model that allows conditional expression of human PLTP. In this mouse model a human PLTP encoding sequence is controlled by a Tet-On system. Upon induction of PLTP expression, our mouse model showed a strongly increased PLTP activity (from 3.0 ± 0.6 to 11.4 ± 2.8 AU, p < 0.001). The increase in PLTP activity resulted in an acute decrease in plasma cholesterol of 33% and a comparable decrease in phospholipids. The decrease in total plasma cholesterol and phospholipids was caused by a 35% decrease in HDL-cholesterol level and a 41% decrease in HDL-phospholipid level. These results demonstrate the feasibility of our mouse model to induce an acute elevation of PLTP activity, which is easily reversible. As a direct consequence of an increase in PLTP activity, HDL-cholesterol and HDL-phospholipid levels strongly decrease. Using this mouse model, it will be possible to study the effects of acute elevation of PLTP activity on lipoprotein metabolism and pre-existing atherosclerosis.

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Tet system in the brain: Transgenic rats and lentiviral vectors approach

Konopka¹,

Duniec²,

Klejman³

et al. 2009

Genesis

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Local and regulated expression of exogenous genes in the central nervous system is one of the major challenges of modern neuroscience. We have approached this issue by applying the inducible tetracycline system to regulate the expression of EGFP reporter gene in double transgenic rats. We have obtained a strong induction of EGFP only in male testes, which correlated with a high level of rtTA expression only in this organ. To overcome the problem of lack of rtTA protein in the transgenic rat brain, we have delivered this Tet system activator with lentiviral vectors into the dentate gyrus of hippocampus of transgenic EGFP rats. As a result, after systemic application of doxycycline we have obtained inducible, stable and restricted to the desired brain region expression of EGFP. An advantage of this strategy is that the transgene is located in the same genetic milieu in every cell of the transgenic organism. This is crucial to obtain uniform expression of the regulated gene within the target brain structure. Combination of rat transgenesis and lentiviral vectors is a novel approach enabling precise spatiotemporal regulation of genes of interest strictly in the brain structure of choice or in other tissues.

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Pharmacokinetics and tissue localization of doxycycline polyphosphate and doxycycline hydrochloride in the rat

Cited by 15 publications

References 11 publications

Pharmacokinetics of doxycycline in broiler chickens

Pharmacokinetics of doxycycline in broiler chickens

Inducible expression of phospholipid transfer protein (PLTP) in transgenic mice: acute effects of PLTP on lipoprotein metabolism

Tet system in the brain: Transgenic rats and lentiviral vectors approach

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