Clinical Pharmacokinetics of Doxycycline and Minocycline

Saivin, Sylvie; Houin, Georges

doi:10.2165/00003088-198815060-00001

Cited by 313 publications

(237 citation statements)

References 33 publications

Supporting

Mentioning

222

Contrasting

Unclassified

Order By: Relevance

“…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.

304

184

View full text Add to dashboard Cite

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.

304

184

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…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

View full text Add to dashboard Cite

Clinical Pharmacokinetics of Doxycycline and Minocycline

Cited by 313 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

Contact Info

Product

Resources

About