Clinical Pharmacokinetics of Doxycycline and Minocycline

Saivin, Sylvie; Houin, Georges

doi:10.2165/00003088-198815060-00001

Cited by 319 publications

(237 citation statements)

References 33 publications

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“…Furthermore, the significant functional improvement after SCI was achieved by the systemic administration of minocycline at 1 h p.i., a time window that is practical for administering the drug in the field. Therefore, our results, together with the safety record of minocycline and its ability to penetrate the blood-brain barrier (51), suggest that it may become a clinical therapy for SCI.…”

Section: Discussionmentioning

confidence: 64%

Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury

Teng

Choi

Onario

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

307

184

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We investigated whether permeability transition-mediated release of mitochondrial cytochrome c is a potential therapeutic target for treating acute spinal cord injury (SCI). Based on previous reports, minocycline, a second-generation tetracycline, exerts neuroprotection partially by inhibiting mitochondrial cytochrome c release and reactive microgliosis. We first evaluated cytochrome c release at the injury epicenter after a T10 contusive SCI in rats. Cytochrome c release peaked at Ϸ4 -8 h postinjury. A dose-response study generated a safe pharmacological regimen that enabled i.p. minocycline to significantly lower cytosolic cytochrome c at the epicenter 4 h after SCI. In the long-term study, i.p. minocycline (90 mg͞kg administered 1 h after SCI followed by 45 mg͞kg administered every 12 h for 5 days) markedly enhanced long-term hind limb locomotion relative to that of controls. Coordinated motor function and hind limb reflex recoveries also were improved significantly. Histopathology suggested that minocycline treatment alleviated later-phase tissue loss, with significant sparing of white matter and ventral horn motoneurons at levels adjacent to the epicenter. Furthermore, glial fibrillary acidic protein and 2 ,3 cyclic nucleotide 3 phosphodiesterase immunocytochemistry showed an evident reduction in astrogliosis and enhanced survival of oligodendrocytes. Therefore, release of mitochondrial cytochrome c is an important secondary injury mechanism in SCI. Drugs with multifaceted effects in antagonizing this process and microgliosis may protect a proportion of spinal cord tissue that is clinically significant for functional recovery. Minocycline, with its proven clinical safety, capability to cross the blood-brain barrier, and demonstrated efficacy during a clinically relevant therapeutic window, may become an effective therapy for acute SCI.

show abstract

Section: Discussionmentioning

confidence: 64%

Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury

Teng

Choi

Onario

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

307

184

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“…this compound is widely distributed in the body. This results in tissue concentrations that exceed serum concentrations [40]. Moreover, lipid-soluble tetracyclines have been reported to accumulate in leucocytes [9,41,42].…”

Section: Discussionmentioning

confidence: 99%

The influence of tetracyclines on T cell activation

Kloppenburg

Verweij

Miltenburg

et al. 1995

Clinical and Experimental Immunology

106

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SUMMARYMinocycHne has been shown to have an anti-inflammatory effect in patients with rhetimatoid arthritis (RA). Since there is evidence thai RA is a T cell-mediated disease, we investigated Ihe efl'ect of minocycline on human T cell clones derived from the synovium of an RA patient. The T cells, when activated via the T cell receptor {TCR)/CD3 complex, were suppressed functioniiUy by minocyciine, resulting in a dose-dependent inhibition of T eell proliferation and reduction in production of lL-2. inlerferon-gamma (IFN-7) and tumour necrosis faetor-alpha (TNF-Q). Besides an inhibition of IL-2 production, mitiocycline exerted its effect on T cell proliferation by induction of a decreased IL-2 responsiveness. We showed that the ehelating capacity of minocycline plays a crucial role in the inhibitory effect on T eell function, since the inhibitory elTecl on T cell proliferation could be annulled hy addition of exogenous Ca^^. However, minocycline did nol markedly influence the typical TCR/CD3-induced intracellular Ca^* mobilization. Taken together. Ihe results elearly indicate that minocycline has immunomodulating effects on human T cells.

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“…Minocycline is distinguishable from other tetracycline for its highly lipophilic nature; it is a superior blood-brain barrier penetrator compared to the other tetracycline, including doxycycline [19]. It has properties, discussed below, that are outside of its antibiotic abilities.…”

Section: Minocyclinementioning

confidence: 99%

“…In 1988, Saivin and Houin [19] described the pharmacokinetics of minocycline. The 200mg dose, which is the standard used in many of the studies conducted, yields a peak concentration of 6mg/L in humans.…”

Section: Treatment With Minocycline In Humansmentioning

confidence: 99%

Minocycline: A Novel Stroke Therapy

Møller¹

2015

JNSK

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Clinical Pharmacokinetics of Doxycycline and Minocycline

Cited by 319 publications

References 33 publications

Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury

Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury

The influence of tetracyclines on T cell activation

Minocycline: A Novel Stroke Therapy

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