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Biomedical subjects

J M Jacquet

Publications and source records attributed to J M Jacquet.

9 recordsLinked to original sources
PubMed1992

Doxorubicin and doxorubicinol plasma concentrations and excretion in parotid saliva.

The pharmacokinetics of doxorubicin (DOX) and doxorubicinol (DOXol) was studied in six patients with various advanced neoplastic diseases who received 28-72 mg/m2 DOX (nine courses). Plasma and parotid saliva were collected over a 48-h period, and DOX and DOXol were quantified by high-performance liquid chromatography with fluorescence detection. As reported previously, a wide range of plasma levels were found among our patients. It appears that in addition to being quickly cleared from the plasma, both DOX and DOXol are excreted in detectable amounts in parotid saliva, a route of elimination that has been given little attention, if any. Excretion in the saliva exposes the mucosa of the upper gastrointestinal tract to drug and may play a role in causing stomatitis in patients receiving DOX by the i.v. route. Since huge interindividual and pronounced intraindividual differences were found in S/P ratios that mostly were not systematically related to the plasma drug concentration, the concentration in parotid saliva was not useful in predicting the level of free DOX and DOXol in plasma. For the parent drug and its metabolite, the S/P ratios increased significantly with time during the 48-h period after dosing.

Adult↗
PubMed1992

A sensitive and reproducible HPLC assay for doxorubicin and pirarubicin.

A high-performance liquid chromatographic method with spectrofluorometric detection has been developed for the analysis of doxorubicin (DOX), pirarubicin (PIRA) and their metabolite, doxorubicinol, in plasma. The detection was performed at 480 nm for excitation, and 590 nm for emission. The proposed technique is selective, reliable, and sensitive. The limit of quantification was 2 ng ml-1 for DOX and 5 ng ml-1 for PIRA. The reproducibility of the analytical method through statistical coefficients is approximately 5%. The accuracy of the method is good; the relative error is less than 5%.

Antibiotics, Antineoplastic↗
PubMed1991

Bayesian estimation of doxorubicin pharmacokinetic parameters.

Doxorubicin was given by brief i.v. infusion (doses ranging from 25 to 72 mg/m2) to 28 patients for 2-7 successive courses of chemotherapy (68 courses studied in all). A Bayesian approach was developed to determine the individual pharmacokinetic parameters of doxorubicin. Statistical characteristics of the population pharmacokinetic parameters were first evaluated for 19 patients and a total of 30 courses, which, when combined with 4 individual plasma concentrations of drug, led to a Bayesian estimation of individual pharmacokinetic parameters for the remaining 38 courses. The estimated parameters for the elimination phase (A3/V1 and t1/2 elimination) and the residual plasma level at 48 h as computed by Bayesian estimation on this reduced sub-optimal sampling protocol were compared with a maximal likelihood estimation of these parameters. No statistically significant differences were found. Performance of the developed methodology was evaluated by computing bias and precision. The mean errors were -0.0315 x 10(-4) l-1 for A3/V1, 0.0839 h for t1/2 elimination, and -0.22 ng/ml for c(48 h). The precision of the prediction of these three parameters (0.304 x 10(-5) l-1, 3.34 h, and 0.659 ng/ml, respectively) remained lower than the interindividual standard deviation (1.42 x 10(-4) l-1, 14.9 h, and 4.54 ng/ml, respectively). This procedure enables the estimation of individual pharmacokinetic parameters for doxorubicin at minimal cost and minimal disturbance of the patient.

Bayes Theorem↗
PubMed1990

Doxorubicin and doxorubicinol: intra- and inter-individual variations of pharmacokinetic parameters.

Doxorubicin was given by short i.v. infusion (dose range 25-72 mg/m2) to 18 patients who underwent three to seven successive courses of chemotherapy (total, 57 courses). Plasma levels of doxorubicin and its major metabolite doxorubicinol were determined by high-performance liquid chromatography over a 48-h period after the infusion. Pharmacokinetic parameters for the parent drug and its metabolite were calculated for each course of treatment. The results show considerable inter- and intraindividual variations for most parameters. The coefficients of variation (CV) ranged from 37% to 93% (inter-individual) and from 6% to 59% (intra-individual). Nevertheless, we observed a good stability over successive courses for terminal half-life in six patients (CV, 6%-25%) and for clearance and AUC in four subjects (CV, 10%-22%). The ratio of the AUCs for doxorubicinol: doxorubicin averaged 0.514. The pharmacokinetic pattern of doxorubicinol was biphasic in plasma of the majority of patients. We propose a model for curve-fitting of these metabolite plasma concentrations that is based on two successive releases of the compound in the plasma compartment, separated by a lag time.

Adult↗
PubMed1988

Long-term effects of pinealectomy on testicular function, luteinizing hormone-releasing hormone hypothalamic system, and plasma prolactin levels in the mink, a short-day breeder.

Experiments in minks, as in a number of other seasonal breeders, clearly demonstrate that the pineal gland is essential for the photoperiodic control of reproduction. While maintenance of pineal-intact minks under natural photoperiods results in a set of seasonally appropriate changes in testicular activity, pinealectomized minks undergo none of these changes but rather remain sexually inactive as under long-day conditions. Thus, the consequences of pinealectomy differ from one photoperiodic species to another, but the unifying feature is the organism's need for the pineal gland to respond appropriately to changes in day length. Although the precise mechanism by which the pineal regulates hypothalamic-pituitary gonadal function remains unknown, the results of the present study indicate that, in the mink, luteinizing hormone-releasing hormone axonal transport is affected by pinealectomy. Furthermore, our results suggest that the pineal does not act exclusively upon the neuroendocrine-gonadal system but also acts on other functions that are influenced by photoperiod. Pinealectomized minks left in natural conditions cannot adjust their prolactin secretion in response to either long or short photoperiods. Operated animals continued to have plasma prolactin variations but at irregular intervals and with no apparent relation to the time of the year. The data strengthen the hypothesis that melatonin may act at some point on the hypothalamic neuroendocrine systems, which regulate the two functions differently, and that melatonin is not an anti- or progonadal substance but rather a seasonal transducer.

Animals↗
PubMed1986

Circadian participation in the photoregulation of testis activity and prolactin secretion in the mink, a short-day breeder.

It has been demonstrated that an endogenous mechanism is involved in photoperiodic time measurement in the mink, a short-day-breeding mannal. A study of testicular activity (testicular volume, plasma testosterone concentration) and plasma prolactin level was carried out in sexually resting minks (the experiment began in November). Groups of minks were kept in the natural photoperiod or subjected to different resonance light-dark (LD) cycles (LD 4:8, LD 4:20, LD 4:32, LD 4:44); an additional group of animals was reared in an ahemeral photoperiod (LD 4:16). A rapid increase of testicular activity was observed in control animals or those kept in LD 4:20 (T 24) and LD 4:44 (T 48). In the other groups of animals, those kept in LD 4:8 (T 12), LD 4:32 (T 36), and LD 4:16 (T 20), testicular function remained at rest. Prolactin secretion was, in contrast, stimulated in the groups kept in LD 4:8 (T 12). LD 4:32 (T 36), and LD 4:16 (T 20), and remained low in the groups kept in LD 4:20 (T 24) and LD 4:44 (T 48). These results show that the effects of the different photoperiodic regimens do not depend on the duration of the photophase, but rather on the period of the LD cycles. The LD cycles that allow an increase of testicular function are those that are inhibitory to reproduction in birds and long-day-breeding mammals. To explain these results, it is suggested that in the mink exposure to light during the circadian photosensitive phase induces inhibition of testicular activity and stimulation of prolactin secretion. To explain the opposite effects of a single photoperiod on testicular function and secretion of prolactin, the hypothesis has been advanced that, in the mink, long days might simultaneously inhibit hypothalamic luteinizing-hormone-releasing hormone (LH-RH) activity and prolactin-inhibiting factor (PIF) activity.

Animals↗
PubMed1986

[Effect of thyroidectomy on variations during the spring and summer of the testicular activity and blood prolactin in the mink].

The possible role of thyroid hormones in the setting of sexual quiescence was investigated in the mink, since levels of thyroid hormones were earlier shown to rise while testicular activity decreased. When performed at the beginning of the sexual period, thyroidectomy transiently stimulated testosterone production, and significantly prolonged the duration of maximal testicular development. These results indicate that mink conforms to a pattern of inhibitory thyroid-testis interactions similar to that previously described in several species of birds and mammals. Thyroidectomy was unable, however, to prevent ultimately the installation of sexual quiescence which also appears independent of the photoperiod. On the other hand, thyroidectomy did not modify, from February to October, the general pattern of prolactin secretion, even though the vernal stimulation of prolactin secretion, induced by increasing daylength, was significantly enhanced in the absence of thyroid hormones.

Animals↗