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Biomedical subjects

P A Shetty

Publications and source records attributed to P A Shetty.

At least 19 recordsLinked to original sources

Pharmacokinetics of methotrexate in Indian children and its relationship to nutritional status.

Any significant change in the pharmacokinetics of an anticancer drug would have a bearing on its therapeutic efficacy and toxicity. Nutritional deficiencies have been shown to affect the pharmacokinetics of a drug. Since malnutrition and undernutrition are widely prevalent in India, the effect of initial nutritional status on the overall kinetics of methotrexate (MTX) administered to cancer patients appeared to be of practical importance. A study of 6 Indian children with malignancies was made to examine the pharmacokinetics of low dose MTX and its relationship to the nutritional status. The results indicate that the relative weight correlates well with the anthropometric parameters, nutritional parameters and dietary intake and may be used as a marker of nutritional status.

Adolescent↗

Clinical significance of heat labile Regan isoenzyme variant in Hodgkin's disease.

The activity of a heat labile variant of Regan type alkaline phosphatase (HLRI) was studied in the serum of 38 histologically proved patients with Hodgkin's disease. The activity was also studied in 40 normal healthy adults matched for age and sex as control. HLRI was significantly elevated in patients with Hodgkin's disease in comparison with normal controls (1.12 +/- 0.12 units/ml vs 0.09 +/- 0.01 units/ml; P less than 0.001). The mean values of the isoenzyme tended to increase progressively with increasing stages of disease, reflecting a significant linear trend (P less than 0.001). The serial measurement of this variant may serve as a useful parameter in assessing disease activity and response to chemotherapy.

Adult↗

Pharmacokinetics of methotrexate in adult Indian patients and its relationship to nutritional status.

Since anticancer drugs have a low therapeutic index, any significant change in the pharmacokinetics of a drug would have a bearing on therapeutic efficacy and drug toxicity. Nutritional deficiencies have been shown to affect the four processes of pharmacokinetics, ie, absorption, distribution, biotransformation, and excretion. Malnutrition and undernutrition are widely prevalent in India and thus it was thought to be of practical importance to study the effect of initial nutritional status on the overall kinetics of methotrexate, a widely used anticancer drug. The results of the study reveal that relative weight correlates well with the anthropometric parameters, nutritional parameters, and dietary intake and may be used as a marker of nutritional status. When grouped on the basis of relative weights, the undernourished patients revealed a significant (P less than 0.01) prolongation of biological half-life and a significant (P less than 0.001) reduction in clearance. Based on these results, relative weight has been proposed as a basis for drug dosage determinations in place of the existing practice of administering antineoplastic drugs on the basis of body surface area or body weight alone.

Adult↗

Urinary 6-hydroxymethylpterin levels accurately monitor response to chemotherapy in acute lymphoblastic leukemia.

We have recently shown that the levels of urinary 6-hydroxymethylpterin are highly elevated (3 to 20 fold) in a variety of human malignancies as compared to its urinary excretion in patients with nonmalignant diseases or normal healthy subjects. In the subsequent studies, this parameter has been shown to be a reliable index for accurately monitoring the response of patients with acute myeloblastic leukemia (AML) during chemotherapy. In this study, the excreted urinary levels of 6-hydroxymethylpterin as well as the bone marrow lymphoblast values were measured simultaneously in four patients with acute lymphoblastic leukemia (ALL) during antileukemic therapy. Various drug regimens employed for treatment have also been indicated. A good correlation was seen between urinary pterin levels and % blasts during treatment, thus accurately monitoring remission or relapse of the disease in response to the antileukemic therapy. These results again conclusively show that the simple noninvasive determination of 6-hydroxymethylpterin provides a reliable index of the total tumor load in acute lymphoblastic leukemic cases undergoing treatment.

Adolescent↗

Modified combination chemotherapy of leukemia. An attempt to overcome drug resistance.

Vincristine and prednisolone are important drugs for induction therapy in acute lymphoblastic leukemia. In our experience quite a number of patients relapse during maintenance therapy after induction. At this stage some of the patients are resistant to vincristine and prednisolone. In the present study we attempted to explore whether vincristine could be used together with cytosine arabinoside. Vincristine being a phase-specific agent is known to synchronize the leukemic cells in vitro and a drug like cytosine arabinoside added after vincristine at the appropriate time is expected to have added cell kill. In vitro studies with leukemic cells confirmed the expected increase in cell kill with the addition of cytosine arabinoside 6 h after vincristine treatment. Simultaneously, the same approach was explored in the clinic. Acute lymphoblastic leukemia patients who were resistant to vincristine and prednisolone for reinduction, remitted with this strategy, i.e. with the addition of cytosine arabinoside 6 h after the vincristine treatment.

Adolescent↗

Urinary 6-hydroxymethylpterin levels accurately monitor response to chemotherapy in acute myeloblastic leukemia.

In our earlier study it was shown that patients with various types of cancer excrete three- to 20-fold higher levels of urinary 6-hydroxymethylpterin as compared to patients with nonmalignant diseases or normal volunteers. In the present study urinary 6-hydroxymethylpterin levels have been measured as an index of disease status in acute myeloblastic leukemic patients on antileukemic drugs. The daily excretory pterin levels and the values of respective blast counts have been graphically presented for four cases with the chemotherapeutic regimens. Remission of the disease was marked by a rapid drop in the urinary 6-hydroxymethylpterin levels and correlated very well with the percentage of blasts. In another study the percentage of blasts and the urinary 6-hydroxymethylpterin were determined simultaneously in four patients undergoing chemotherapy. The data conclusively show that the simple noninvasive determination of urinary 6-hydroxymethylpterin levels accurately and rapidly reflects the status of the disease under treatment and could conveniently be employed as a suitable index for monitoring the effect of chemotherapy as well as the condition of the residual extramedullary leukemic infiltration.

Antineoplastic Agents↗