LP-10 Publications

Innovative use of intravesical tacrolimus for hemorrhagic radiation cystitis

Int. Urol. Nephrol. DOI 10.1007/s11255-015-1098-6. September 2015

We present an 81-year-old man with a history of localized prostate cancer, which was treated with external beam radiation therapy and subsequently developed severe hemorrhagic radiation cystitis for which he has failed several treatments. We present the novel use of intravesical tacrolimus for the treatment of refractory radiation cystitis and gross hematuria. The patient tolerated the treatment well, and it resulted in the resolution of his gross hematuria without further consideration for formalin instillation or cystectomy and diversion. Intravesical tacrolimus is a safe, minimally invasive, and promising treatment option for radiation hemorrhagic cystitis.



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Intravesical Liposomal Tacrolimus Protects Against Radiation Cystitis Induced by 3-Beam Targeted Bladder Radiation

J. Urol. 194, 578-84 August 2015

A rat radiation cystitis model was developed using radiation from a CT scanner. Bladder irritation and treatment-induced recovery was measured via the the measurement of inter-micturition intervals following radiation and treatment for extended multi-day periods. LP-10 was shown to positively affect radiation-induces symptoms. The image shown on the left is histology of urothelia and bladder walls from two rats. The left image was from a control rat that was treated with a saline instillation. The right image was from a rat treated with a LP-10 instillation. Note that the urothelium is intact in the LP-10 treated animal but not the control animal.

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Development of Potential Orphan Drug Therapy of Intravesical Liposomal Tacrolimus for Hemorrhagic Cystitis Due to Increased Local Drug Exposure

J. Urol. 189, 1553-1558, 2013

The potent immunosuppressive effect of systemic tacrolimus is limited by the high incidence of severe adverse effects, including nephrotoxicity and hypertension. Intravesical application of tacrolimus is hindered by its poor aqueous solubility, justifying the search for novel delivery platforms such as liposomes. A single dose of lipo-tacrolimus (LP-10) was instilled in the bladder with the rat under anesthesia. Also, tacrolimus was instilled intravesically or injected intraperitoneally in other rat groups. The AUC of lipo-tacrolimus in serum at 0 to 24 hours was significantly lower than that of tacrolimus instillation or injection. Noncompartmental pharmacokinetic data analysis revealed maximum concentration of lipo-tacrolimus (LP-10) and tacrolimus in serum and urine at 1 and at 2 hours, respectively. Urine after intravesical administration was significantly higher than in the intraperitoneal group. Bladder tacrolimus did not differ significantly between the groups.

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Intravesical Immune Suppression by Liposomal Tacrolimus in Cyclophosphamide-Induced Inflammatory Cystitis

Neurourol Urodyn 15 June 2010

Adult female Sprague-Dawley rats (N = 52) divided into 4 groups were injected with cyclophosphamide (CYP) (200 mg/kg, ip) except for sham (saline injection, ip). Other three groups were instilled with either saline (1 cc, retained for 1 hr), liposome (LP- 1 cc) or liposomal encapsulated tacrolimus (LP-10) (LFK- 0.2 mg tacrolimus/1 ml LP). Baseline cystometrogram (CMG) was performed on day 1 and day 3. Rats treated with LFK (LP-10) demonstrated suppression of bladder overactivity.

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Advances in Therapeutic Development for Radiation Cystitis

LUTS 17 October 2013

Radiation cystitis is described as well as its current treatment options. Many of the drawbacks of existing options are noted. A brief description of tacrolimus as a therapeutic option is also provided, including liposomal tacrolimus (LP-10).

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