Circulating Levaquin leaves the bloodstream, deposits in Achilles’ tendons, and alters tendon cells
Posted by
Armand RossettiDecember 02, 2008 10:42 AMBoth short and long term treatment with fluoroquinolone antibiotics may cause tendon matrix alteration that can lead to tendinopathy with subsequent rupture. Tendinopathy is newer all-inclusive medical term that encompasses tendonitis, tendonosis and tendon rupture.
Structure:
Tendons are tropocollagen connective tissue bundles that attach muscle to bone. Stress between bone and muscle is longitudinal. That is why chains of tropocollagen combine to make longitudinally arranged fibers that bundle together as fibrils. Groups of fibrils form endotenon covered groups of fascicles that have a loose connective tissue packing called the epitenon which also contains blood vessels. Here is a drawing.
The Achilles’ tendon is the largest tendon in the body and please bear in mind that it has a limited blood supply. The Achilles is also the strongest and toughest tendon and capable of lifting the entire body weight against a severely adverse leverage ratio.
Toxicity:
It is interesting to note that 7 – 10 days after a tendon injury, there is little or no inflammatory response. Likewise, 2 – 3 weeks after fluoroquinolone ingestion, no inflammatory cells are present.
The toxic effects of fluoroquinolones cause dysplasia (abnormal cell development and maturation) of a tendon’s collagen fibrils leading to a reduction in tensile strength (the tendon’s ability to stretch and not rupture). Reportedly, fluoroquinolones, such as Levaquin alter the amount of glycoproteins found in tendon cells and fragment nuclear DNA apoptosis markers. DNA fragmentation may explain fluoroquinolone-induced tendinopathy.
In addition, investigators have reported that fluoroquinolone drugs, such as Levaquin, can cause biochemical changes (affecting magnesium chelation). Reportedly, those biochemical changes interfere with the process that contributes to tendon healing (proteoglycan synthesis). As a result of those changes, Levaquin ingestion has the same physiological characteristics as tendon overuse, and that conclusion is evident because of the presence of giant cells and structural abnormalities in tenocytes (tendon cells).
Distribution:
Fluoroquinolones leave the bloodstream, deposit in tendons, and cause localized tendon toxicity (Meissner, A., Borner, K., & Koeppe, P. (1990); Concentration of ofloxacin in human bone and cartilage, Journal of Antimicrobials and Chemotherapy). Therefore, Levaquin takes up residence at the very site that it affects.
A Thought:
In light of all of the above, the FDA has extended marketing “pediatric exclusivity” to Ortho-McNeil for Levaquin based on five company-sponsored pediatric studies that the FDA requested.