Intravenous Dosing Conditions May Affect Systemic Clearance for Highly Lipophilic Drugs: Implications for Lymphatic Transport and Absolute Bioavailability Studies

2012 ◽  
Vol 101 (9) ◽  
pp. 3540-3546 ◽  
Author(s):  
Suzanne M. Caliph ◽  
Natalie L. Trevaskis ◽  
William N. Charman ◽  
Christopher J.H. Porter
Keyword(s):  
Absolute Bioavailability ◽  
Lymphatic Transport ◽  
Systemic Clearance ◽  
Lipophilic Drugs

Pharmacokinetic, oral bioavailability, and safety study of fluorouracil in patients treated with 776C85, an inactivator of dihydropyrimidine dehydrogenase.

1996 ◽  
Vol 14 (12) ◽  
pp. 3085-3096 ◽  
Author(s):  
S D Baker ◽  
S P Khor ◽  
A A Adjei ◽  
M Doucette ◽  
T Spector ◽  
...  
Keyword(s):  
Dihydropyrimidine Dehydrogenase ◽  
Kinetic Studies ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Oral Solution ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Studies ◽  
Systemic Clearance ◽  
Calculated Creatinine Clearance ◽  
Apparent Volume Of Distribution

PURPOSE To study the absolute bioavailability and pharmacokinetics of an oral solution of fluorouracil (5-FU) in patients treated with 776C85, an oral inactivator of dihydropyrimidine dehydrogenase (DPD), and to evaluate the feasibility of administering oral 5-FU and 776C85 on a multiple-daily dosing schedule. PATIENTS AND METHODS Twelve patients with refractory solid tumors were enrolled onto this three-period study. In periods 1 and 2, patients were randomly assigned to treatment with 5-FU 10 mg/m2 on day 2 given by either the oral or intravenous (IV) route with oral 776C85 3.7 mg/m2/d on days 1 and 2. In period 3, patients received escalating doses of 5-FU (10 to 25 mg/ m2/d) orally for 5 days (days 2 to 6) with 776C85 3.7 mg/m2/d orally (days 1 to 7) every 4 weeks. Pharmaco-kinetic studies were performed in periods 1 and 2, and after the fifth oral dose of 5-FU in period 3. RESULTS Twelve patients completed the bioavailability and pharmacokinetic studies. Following oral 5-FU 10 mg/m2, the bioavailability was 122% +/- 40% (mean +/- SD), the terminal half-life (t1/2 beta) was 4.5 +/- 1.6 hours, the apparent volume of distribution (V beta) was 21.4 +/- 5.9 L/ m2, and the systemic clearance (Clsys) was 57.6 +/- 16.4 mL/min/m2. A correlation was observed between oral 5-FU systemic clearance and calculated creatinine clearance (r = .74; P = .009). Multiple-daily dosing did not appear to affect the pharmacokinetics of oral 5-FU. Neutropenia was the principal toxicity of oral 5-FU and 776C85, precluding escalation of oral 5-FU to doses greater than 25 mg/m2/d for 5 days every 4 weeks with 776C85. CONCLUSION The oral DPD inactivator 776C85 enables oral administration of 5-FU and may alter conventional 5-FU administration practices.

Effect of abdominal surgery on the intestinal absorption of lipophilic drugs: possible role of the lymphatic transport

2009 ◽  
Vol 153 (6) ◽  
pp. 296-300 ◽  
Author(s):  
Pavel Gershkovich ◽  
Constantin Itin ◽  
Avihai Yacovan ◽  
Shimon Amselem ◽  
Amnon Hoffman
Keyword(s):  
Abdominal Surgery ◽  
Intestinal Absorption ◽  
Lymphatic Transport ◽  
Lipophilic Drugs

The Impact of Lymphatic Transport on the Systemic Disposition of Lipophilic Drugs

2013 ◽  
Vol 102 (7) ◽  
pp. 2395-2408 ◽  
Author(s):  
Suzanne M. Caliph ◽  
Enyuan Cao ◽  
Jürgen B. Bulitta ◽  
Luojuan Hu ◽  
Sifei Han ◽  
...  
Keyword(s):  
Lymphatic Transport ◽  
Lipophilic Drugs ◽  
The Impact ◽  
Systemic Disposition

Sentinel lymph node diagnostic in prostate carcinoma: Part II: Biokinetics and dosimetry of 99mTc-Nanocolloid after intraprostatic injection

2002 ◽  
Vol 41 (02) ◽  
pp. 102-107 ◽  
Author(s):  
J. Kopp ◽  
H. Vogt ◽  
F. Wawroschek ◽  
S. Gröber ◽  
R. Dorn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Urinary Bladder ◽  
Lymph Nodes ◽  
Effective Dose ◽  
Residual Activity ◽  
Tracer Uptake ◽  
Lymphatic Transport ◽  
Radionuclide Distribution ◽  
Radioactivity Uptake

Summary Aim: To visualise the sentinel lymph nodes (SLNs) of the prostate we injected the radiotracer into the parenchyma of the prostate. The activity was deposited in liver, spleen, bone marrow, urinary bladder and regional lymphatic system. The aim of this work is to determine biokinetical data and to estimate radiation doses to the patient. Methods: The patients with prostate cancer received a sonographically controlled, transrectal administration of 99mTc-Nanocoll®, injected directly into both prostate lobes. In 10 randomly selected patients radionuclide distribution and its time course was determined via regions of interest (ROIs) over prostate, urinary bladder, liver, spleen and the lymph nodes. The uptake in the SLNs was estimated from gamma probe measurements at the surgically removed nodes. To compare tumour positive with tumour free lymph nodes according to SLN-uptake and SLNlocalisation we evaluated 108 lymph nodes out of 24 patients with tumour positive SLN. For calculating the effective dose according to ICRP 60 of the patients we used the MIRD-method and the Mirdose 3.1 software. Results: The average uptake of separate organs was: bladder content 24%, liver 25.5%, spleen 2%, sum of SLN 0.5%. An average of 9% of the applied activity remained in the prostate. The residual activity was mainly accumulated in bone marrow and blood. Occasionally a weak activity enrichment in intestinal tract and kidneys could be recognized. The effective dose to the patient was estimated to 7.6 μSv/MBq. The radioactivity uptake of the SLN varied in several orders of magnitude between 0.006% and 0.6%. The probability of SLN-metastasis was found to be independent from tracer uptake in the lymph node. The radioactivity uptake of the SLNs in distinct lymph node regions showed no significant differences. Conclusion: The radiotracer is transferred out of the prostate via blood flow, by direct transfer via the urethra into the bladder and by lymphatic transport. Injecting a total activity of 200 MBq leads to a mean effective dose of 1.5 mSv. It is not recommended to use the tracer uptake in lymph nodes as the only criterion to characterize SLNs.

scholarly journals Absorption and lymphatic transport of cholesterol in the rat

1968 ◽  
Vol 9 (5) ◽  
pp. 596-601
Author(s):  
Christer Sylvén ◽  
Bengt Borgström
Keyword(s):  
Lymphatic Transport
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