Controlled-release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies.

Several controlled-release carbidopa/levodopa preparations have been formulated to achieve a more stable and extended antiparkinsonian action. The most effective is Sinemet CR (Sinemet CR4), with an erodible polymer matrix that retards release of levodopa. In 19 parkinsonians with prominent dose-by-dose fluctuations, double-blind crossover trials comparing 8-week regimens of standard carbidopa/levodopa (25/100) to Sinemet CR (50/200) showed comparable clinical outcomes, with mean daily dosing for optimal control reduced from 10.2 to 5.4 (although mean daily levodopa dosage increased from 1,340 to 1,781 mg/day). Most patients improved on the Sinemet CR regimen in hours "on" and in ratings of clinical state and disability. With pharmacokinetic studies correlated to clinical ratings, plasma levodopa was less variable during Sinemet CR treatment, and clinical responses showed greater uniformity. Compared to standard Sinemet 25/100, time to peak levodopa concentration (2.3 versus 1.1 hrs), onset of maximal clinical improvement (2.2 versus 1.1 hrs), and other indices were significantly delayed with Sinemet CR. Levodopa bioavailability and clearance were similar between formulations. Although onset of clinical response is slower, the Sinemet CR formulation lessens peak-dose and "wearing-off" responses occurring with conventional carbidopa/levodopa and offers substantial improvement for some parkinsonians.

Pharmacokinetic and pharmacodynamic modeling of L-dopa plasma concentrations and clinical effects in Parkinson's disease after Sinemet.

Eleven parkinsonian patients participated in a pharmacokinetic/pharmacodynamic study in an attempt to model levodopa (L-DOPA) plasma concentrations to clinical effect. Carbidopa 25 mg/L-DOPA 100 mg (Sinemet 25/100) was given orally, and blood samples were obtained before and serially for 4 hours after the dose. Effect measurements were obtained with each blood sample and included tapping score, timed walking, and global assessment of motor function. Mean L-DOPA plasma concentrations were fitted to a one-compartment pharmacokinetic model. A time-wise plot of modeled plasma L-DOPA concentrations versus mean effect measurements revealed a counter-clockwise hysteresis. Effect compartment concentrations were determined by a least squares approach, which determined elimination rate constants by minimizing hysteresis. Half-times for the equilibration between plasma and the effect compartment were 0.39 h for tapping, 0.36 h for walking, and 0.34 h for the global score. Pharmacodynamic data were fit best with an Emax model with baseline effect for tapping (Emax = 53.2 taps/60 s, EC50 = 0.58 microgram/ml) and global score (Emax set at 5.0 by limits of scale, EC50 = 2.53 micrograms/ml). A linear model best described the relationship between predicted effect site concentration and timed walking. L-DOPA plasma concentrations after oral Sinemet did not correlate well with clinical response because clinical response lags behind plasma concentrations. Half-times for equilibration between plasma and the effect site were similar for all of the effects measured.

Treatment of inverted nipples using a disposable syringe.

Seven mothers who had inverted nipples were helped to breastfeed their infants with the assistance of a simple device made from a 10 ml disposable syringe. These women were able to successfully breastfeed within one week. On follow-up, these mothers were able to sustain adequate breastfeeding.

Successful induced non-puerperal lactation in surrogate mothers.

Ten surrogate mothers seen between 1986-91 were encouraged to breast-feed their babies varying in age between 8 days to 5 months. All the 10 surrogate mothers had experienced pregnancy and child birth in the past. The lactational gap varied from 1 year to 16 years. Presence of milk was noted on 3rd to 8th day after attempting induced lactation in 5 mothers. No milk was seen on manual expression of the nipple even after 2 weeks in the other 5 surrogate mothers. Two mothers achieved complete breast-feeding and they fed their babies for 2 years. Three mothers could achieve partial lactation and these mothers fed for 1 year or more. All these 5 babies registered satisfactory growth.

Breastfeeding practices in villages of central Karnataka.

OBJECTIVE: To asses the prevailing breastfeeding and infant feeding practices in rural areas. DESIGN: Stratified sampling method in a community based study. SUBJECTS: 1050 infants from 0-24 months of age. RESULTS: The timely first suckling rate was 0.3%. All the infants received prelacteal feeds. Colostrum was rejected by 29% of mothers. Delayed initiation of breastfeeding was common; 35% of babies were not breast-fed even at 48 h of birth. Exclusive breastfeeding was noted in 94% at 1 mo, 83.5% at 2 mo, 72.5% at 3 mo, 61.2% at 4 mo, 43.4% at 5 mo and 26.8% at 6 mo age. Timely complementary feeding rate was 57.3% among infants from 6 to 10 mo age. Continued breastfeeding rate was 99.7% at 1 year and 87.2% at 2 years. The bottle feeding rate was 49.4% among infants below 1 year age. The ever breast-fed rate was 97.0% and the median duration of breastfeeding was beyond 24 months. CONCLUSIONS: Bottle feeding is quite prevalent even in rural areas and the infant feeding practices are far from satisfactory.

PIP: In Central Karnataka in India, a community-based study was conducted on 1050 mothers with infants younger than 24 months to examine breast feeding and infant feeding practices in rural areas. Only 3 infants (0.3%) were offered breastfeeding within 1 hour after delivery. By 72 hours post-delivery, 90.9% of infants had begun breast feeding. All infants had received prelacteal feeds. 28.6% of mothers discarded the colostrum. The exclusive breast feeding rate was 94% at 1 month, 83.5% at 2 months, 72.5% at 3 months, and 61.2% at 4 months. 97% of infants ever breast fed. Among infants younger than 1, 49.4% were bottle fed. Major reasons for introducing bottle feeding were not enough milk (58.1%), subsequent pregnancy (35.8%), and ill health of mother (20.7%). Among infants 6-10 months old, 57.3% had received timely supplementary feedings. 94.7% of mothers used home made weaning foods. 5.3% used commercial foods. These findings show that rural mothers in Central Karnataka delay initiation of breast feeding, reject the colostrum, and use prelacteal foods and that bottle feeding and commercial weaning foods have an influence on infant feeding practices in rural areas.

Follow-up study of survivors of severe protein energy manlnutrition.

OBJECTIVE: To evaluate the nutritional profile of survivors of severe protein energy malnutrition on follow-up at 1-3 years and 5-7 years. DESIGN: Prospective and Cross-sectional point prevalence. METHODS: Group I comprised 50 severely malnourished children dischared 5-7 years from nutritional rehabilitation center and Group II comprised 50 children discharged 1-3 years ago. The nutritional status of these 100 children was compared to the nutritional status of 35 siblings who had not suffered from severe malnutrition in their earlier life (Group III). RESULTS: All the malnourished children showed significant improvement in weight for age. More children in Group I had better height for age compared to Group II(p>0.05). Analysis of weight for height showed that study children has better nutritional status than their siblings who had not suffered from significant malnutrition. CONCLUSION: Significant improvement in nutritional status occurs with nutritional rehabilitation. However, improvement in height for age is more difficult to obtain. Interestingly, rehabilitated malnourished children on follow up had better nutritional status as compared to their siblings.