Hello elias114
HPLC is an analytical technique that allows the level of a specified
substance to be measured very precisely, even when it is only present
in small quantities. It can be used to measure the levels of a drug
in different body components, such as blood plasma, urine and saliva.
This gives an idea of how much of the drug is being retained in the
body and how much is being excreted (this overall picture of what
happens to a drug is known as pharmacokinetics). The pharmacokinetics
of a drug will show some variation between individual patients who
have been given the same dose. This can be due to interaction with
other drugs, and also to individual factors. For example, someone
with kidney damage will excrete drugs more slowly. Someone with liver
damage will be less able to metabolise some drugs into an active form,
or to detoxify toxic drugs. Also, there are genetic differences in
the levels and activity of the enzymes which process different drugs.
Drugs used in cancer chemotherapy tend to be highly toxic. Even
therapeutic doses will often cause some toxic effects, and if the
level becomes a bit higher these effects will become more severe.
Therefore, doctors can use HPLC to monitor chemotherapy in individual
patients so as to ensure that the drug dosage is adjusted to provide a
level in the body that will be therapeutic but cause the minimum
possible level of toxic effects. In addition, if the occurrence of
inevitable toxic effects can be predicted, this enables the early
start of treatments to minimise the symptoms of these effects.
I have found a number of studies to illustrate this, including some
which show how high levels of cancer drugs in saliva are associated
with the development of mucositis. In each case, HPLC was used to
measure the levels of the drug.
In order to find these examples, I searched the medical literature on
Medline at Pubmed http://www.ncbi.nlm.nih.gov/entrez/query.fcgi ,
using the terms 1. HPLC mucositis 2. HPLC monitor chemotherapy
The URL under each article is for the full summary on Medline.
1. Eur J Cancer 2001 Dec;37(18):2357-64
Salivary and plasma pharmacokinetics of topotecan in patients with
metastatic epithelial ovarian cancer.
Boucaud M, Pinguet F, Poujol S, Romieu G, Cupissol D, Astre C, Culine
S, Bressolle F.
Onco-Pharmacology Department, Pharmacy Service, Centre Regional de
Lutte contre le cancer, 34298 Montpellier Cedex 5, France.
The authors looked at drug levels in the saliva and plasma of 13
patients treated with topotecan for ovarian cancer. “Large
patient-to-patient variations in the plasma and saliva concentrations
were observed.” They used the concentrations to find a parameter
called the AUC (area under curve). The AUC value was found to relate
with the degree of myelosuppression (destruction of blood cells)
caused by the drug. “In most cases, abdominal pain occurred in
patients presenting high saliva concentrations. One patient with high
salivary concentrations… had grade 1 mucositis. In conclusion, the
concentration of topotecan in saliva appeared to be useful as an
indirect, non-invasive estimation of the levels of topotecan in the
plasma; thus, saliva concentrations could be a good predictor of the
behaviour of topotecan in the body.”
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11720828&dopt=Abstract
2. Anticancer Drugs 1997 Feb;8(2):119-24
Monitoring of methotrexate and 7-hydroxymethotrexate in saliva from
children with acute lymphoblastic leukemia receiving high-dose
consolidation treatment: relation to oral mucositis.
Albertioni F, Rask C, Schroeder H, Peterson C.
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm,
Sweden.
“The purpose of the study was to find out if saliva concentrations of
methotrexate (MTX) and its main metabolite, 7-hydroxymethotrexate
(7-OHMTX), can predict oral mucositis in children with acute
lymphoblastic leukemia (ALL) after treatment with high-dose
consolidation therapy… Plasma and saliva concentrations of MTX and
7-OHMTX were determined concomitantly by HPLC… The results suggest
that determinations of saliva concentrations of MTX and 7-OHMTX may
predict oral mucositis. This opens up the possibility of early
identification of patients at high risk of developing oral mucositis
in order to intensify topical or systemic treatment of these
patients.”
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9073308&dopt=Abstract
3. Acta Oncol 1998;37(3):277-84
Clinical and pharmacokinetic risk factors for high-dose
methotrexate-induced toxicity in children with acute lymphoblastic
leukemia--a logistic regression analysis.
Rask C, Albertioni F, Bentzen SM, Schroeder H, Peterson C.
Department of Pediatrics, Aarhus University Hospital, Denmark.
The clinical and pharmacokinetic risk factors for toxicity after
high-dose methotrexate (MTX) in children with acute lymphoblastic
leukemia were evaluated… Plasma samples were… analyzed by HPLC to
determine the MTX and 7-hydroxymethotrexate (7-OHMTX)
concentrations... Oral mucositis (WHO grade > or = 1) was
significantly related to a high plasma MTX concentration at 28 h after
starting the infusion (p = 0.013), a low ratio of plasma 7-OHMTX/MTX
at 66 h after starting the infusion (p = 0.049), and a slow clearance
of MTX (p = 0.048)… Increasing age and a long exposure to a high MTX
concentration in plasma (AUC) were significant risk factors… for
developing elevated liver enzymes [this is a sign of liver damage]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9677100&dopt=Abstract
4. Semin Oncol 1994 Oct;21(5 Suppl 8):53-62 Bioanalysis,
pharmacokinetics, and pharmacodynamics of the novel anticancer drug
paclitaxel (Taxol).
Beijnen JH, Huizing MT, ten Bokkel Huinink WW, Veenhof CH, Vermorken
JB, Giaccone G, Pinedo HM.
European Cancer Centre, Amsterdam, The Netherlands.
Several high-performance liquid chromatographic assays have been
reported for the analysis of paclitaxel… Neuropathy, mucositis, and
leukopenia correlate with pharmacokinetic parameters such as area
under the plasma concentration time curve and steady-state paclitaxel
levels.” http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9677100&dopt=Abstract
5. Eur J Cancer 1996 Aug;32A(9):1544-50
Monitoring of asparaginase activity and asparagine levels in children
on different asparaginase preparations.
Boos J, Werber G, Ahlke E, Schulze-Westhoff P, Nowak-Gottl U,
Wurthwein G, Verspohl EJ, Ritter J, Jurgens H.
Department of Paediatric Hematology and Oncology, University of
Munster, Germany.
“The antileukaemic enzyme L-asparaginase is used to achieve the
greatest possible reduction in blood levels of the amino acid
asparagine, an essential factor for the growth of leukaemic blasts…
Faced with increasing reports of treatment complications, we
established a programme to monitor enzyme activity and asparagine
levels in serum… Measurements were made by an enzyme assay and an HPLC
method… When Asparaginase medac is used instead of Crasnitin, and
identical dose will be associated with significantly higher enzyme
activity, well above the level required for complete asparagine
depletion. Clinical studies will need to specify both the preparation
and the dose to be used. When substitution of an alternative drug is
mandatory owing to allergic reactions, monitoring is advisable.”
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8911116&dopt=Abstract
6. Pharm Weekbl Sci 1990 Aug 24;12(4):154-7 Related Articles, Links
A simple high pressure liquid chromatographic method for the
determination of fluorouracil to monitor patients on regional infusion
for hepatic metastases.
Koks CH, Van der Kam HJ, Brouwers JR.
Department of Clinical Pharmacy and Pharmacokinetics, General Hospital
De Tjongerschans, Heerenveen, The Netherlands.
“A rapid and sensitive high pressure liquid chromatographic method has
been developed for the routine monitoring in serum of the
antineoplastic agent fluorouracil, during continuous intraportal
administration.” http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2277762&dopt=Abstract
I hope that this answer has given you the information you require.
Please request clarification if something is unclear. |
