Introduction of papaya leaves has many benefits, among others, for the treatment of cancer, lactation,

digestive problems and dengue fever (Ōtsuki et al. 2010). Herbal tea from the leaves of papaya can
increase platelet in the patients of dengue (Kala 2012). Conatins a variety of components such as the
bioaktif alkaloids, flavonoids, tannins, saponins, carbohydrates, proteins, fats and steroids (Somayaji
2016). The results of the screening there is papaya leaf extract phytochemical compounds, polifenolat
alkaloids, tannins, flavonoids, monoterpen and sesquiterpen (Tjitraresmi et al 2016.). Flavonoids from
the leaves of the papaya extract is a staple item of the main bioaktif from the leaves of the papaya. The
presence of flavonoids in extracts of papaya leaves reaches 0.23% of the results of the flavonoids
isolated from papaya leaf (Musa 2015). Bioaktif components of flavonoids in extracts of the leaves of the
papaya ascertained have been quite diabsorpsi and reach the systemic circulation (Sihabuddin et al.
2011).

Then with or without diekskresi, the drug biotransformation processes from within the body. The entire
process is called pharmacokinetics process and running simultaneously. Pharmacokinetics of the drug
from the drug product is helpful to understand the relationship between physical properties of
fisikokimia of medicinal products and the effects of clinical pharmacology term or effect (Shargel 2012 et
al.). Physiological pharmacokinetics of compound bioaktif in drugs can explain the properties of
absorption, distribution, metabolism, and excretion (ADME) of these compounds in a specific organ or
tissue in the body. Pharmacokinetics parameters through discussing about the correlation of drug in
plasma levels over time in the body, so that may explain the presence of a number of drug in the body at
any given time. Pharmacokinetics parameter describes the effectiveness of the drug can be used to
describe how long the period of effective drug in the body (Wijayanti et al. 2010).

Utilization of papaya leaves as a herbal remedy requires data security, effectiveness, bioavailabilitas and
stability of compound herbal medicine of the bioaktif in the body, through the plasma or serum. Herbal
remedy in question must meet the requirements of quality kefarmasian. Papaya leaf extract as a model
in drug discovery clinical trials must meet the requirements for strengthening data and information in
the framework of industrial development medicinal herbs. Data about the safety and effectiveness of
drugs needed to be consumed by humans, then it should be farmakokinetikanya profiles, studied
include simply applied in blood profiles, patterns of distribution and excretion after administering the
extract of papaya leaves in animals test mice.

Drug kinetics data in the body is very important to determine the relationship between the levels of the
drug in the body at the speed of absorption. Data on drug absorption in the plasma can be used as a
developmental profile of drug levels in the body. Based on the background above, need to do more
research about the levels of flavonoids pharmacokinetics profile of papaya leaf extract is needed in the
development of drugs, particularly the utilization of papaya leaf extract as a medicinal herb.
Data about the safety and effectiveness of substances required to be consumed by humans, then it
should be farmakokinetikanya profiles, studied include simply applied in blood profiles, patterns of
distribution and excretion after administering the extract of papaya leaves on animal testing mice. Data
kinetics of substances in the body is very important to determine the relationship between the levels of
substances in the body by absorption speed. The data absorption substances in plasma can be used as
profile the development levels of substances in the body. Based on the background above, need to do
more research about the levels of flavonoids pharmacokinetics profile of papaya leaf extract is needed
in the development of drugs, particularly the utilization of papaya leaf extract as a medicinal herb.

RESEARCH METHOD of animal research is trying to use the white rats wistar strain male healthy adults
(age 2-3 months) and average weight 215.36 grams. Fourteen rats were divided into 7 groups for blood
sampling in each time series with two times of Deuteronomy (duplo). Mice derived from the Biology lab,
ENGINEERING UNNES. Each rat was used only once per mice or time series in the experiment. Rat
diaklimatisasi (5 days) and after that dipuasakan mice for 12 hours with only water given ad libitum (The
2013 et al.).

Sampling blood Plasma of rats single Doses of papaya leaf extract (900 mg dissolved in 2 mL of aquades)
was given orally. Blood samples were taken as much as 1.5 mL of blood at the time of the series that is
30 minutes, 1 hour, 2 hour, 4 hour, 6 hours, 12 hours, 24 hours after the giving of the papaya leaf
extract. Blood samples are placed in EDTA containing microtube. A blood sample at a speed of 3000 rpm
disentrifuse for 5 minutes (4oC). Blood plasma was taken and stored in the freezer with a temperature
of 20 ° C until testing time (Kanimozi 2016).

Testing the levels of Flavonoids in Extracts of papaya leaves and Plasma content of flavonoids in the
analysis using HPLC-UV VIS C-18 column (150 mm 4.6 mm, 40s pore size 5 µm). Phases of motion that is
used consists of eluen A 27% acetonitrile (solvent A) and eluen B 73% i.e. methanol: acetic acid: water
(8%: 87%: 5%) (solvent B), pH set up 3.64 with acetic acid. Isocratic separations solely under the
condition of constant flow with a speed of 1.5 ml/min. column Temperature 25º C and 347 nm
wavelength

Standard curve creation done by dissolving 1.04 grams Routine in 1000 mL of standard solution of
methanol as a routine. Standard solutions routinely made five different concentrations i.e., 200, 100, 50,
25, 12.5 ppm.
Testing the levels of flavonoids in extracts of papaya leaves are done by dissolving the papaya leaf
extract by weight 0.5 g in 50 ml of methanol. Papaya leaf extract solution is then injected into the HPLC
column. The levels of flavonoids contained in papaya leaf extract gr 900 i.e. 33.903 mg.

Testing of plasma levels of flavonoids by the addition of 1.0 ml of methanol into 0.1 ml of plasma was
then beaten until well blended (homogeneous). Flavonoids in plasma methanol difiltrasi to sterile test
tubes using a 0.45 µm membrane filter (RC-membrane). The filtrate then in injeksikan into the HPLC
column. The results were analyzed using linear regression curve Routine standard dn plasma.
Measurement of plasma levels of Routine in each time series is done. The results obtained with
Microsoft Excel generates a standard curve equation formula.

A statistical analysis of the Parameter of pharmacokinetics includes the Area Under the Curve (AUC), the
maximum concentration (Cmax), time of the attainment of the maximum concentration (Tmax) and half-
life (t1/2). The data obtained were analyzed parameters are descriptive. The data are analyzed by
comparing the levels of flavonoids in the blood plasma of rats based on time series.

A statistical analysis of the Parameter of pharmacokinetics includes the Area Under the Curve (AUC), the
maximum concentration (Cmax), time of the attainment of the maximum concentration (Tmax) and half-
life (t1/2). The data obtained were analyzed parameters are descriptive. The data are analyzed by
comparing the levels of flavonoids in the blood plasma of rats based on time series.

RESULTS and DISCUSSION of the levels of Plasma levels of flavonoids Flavonoids Calculation based on
plasma area samples obtained from HPLC test kromatogram. From the data area five concentrations of
the standard solutions obtained equations standard curve y = 53243x flavonoids – 143400. The results of
the calculation of the levels of flavonoids plasma are presented in Figure 1. Figure 1 shows the process
of rate of absorption and elimination in the body from hour to-0 to 24-hours after the giving of the
papaya leaf extract. During the absorption phase of the curve the plasma levels of flavonoids, the rate of
absorption is greater than the rate of elimination. Phase absorption dominates the plasma levels of
flavonoids curve comparison phase of elimination. From the graph of the plasma levels of flavonoids
against time series calculated the value of the parameter of pharmacokinetics AUC0-t, Ka, and t1/2.
Tmax and Cmax data retrieved directly from the chart.
Figure 1 Graphs the Plasma levels of Flavonoids against Serial time after the grant of 900 mg Papaya leaf
extract per Oral Pharmacokinetics parameters of Flavonoids Extracts of papaya leaves Plasma
pharmacokinetics Data in the form of value of Tmax, Cmax, AUC0-t and t1/2, which describes the
pharmacokinetics the absorption and distribution are presented in table 1. Tmax is the time to gain the
levels peak. Cmax is the peak levels. AUC is the area under the curve and t1/2 is the half-life. Table 1
Data Plasma Pharmacokinetics of flavonoids After grant of 900 mg Papaya leaf extract per Oral

Pharmacokinetics parameter calculation that is obtained from the graph of the plasma levels of
flavonoids against time series. Pharmacokinetics parameter values t1/2 is obtained from the formula
t1/2 = 0,693/K parameter values pharmacokinetics AUC0-t is obtained from the sum of each area
between two consecutive intervals on a chart of the plasma levels of flavonoids against using time series
trapezoid formula. The value of Tmax and Cmax obtained from observations of Figure 1. Overall the data
in table 1 is the values of the plasma pharmacokinetics profile of flavonoids after administering the
extract of papaya leaves.

Pharmacokinetics describes the parameters of the discussion of the effectiveness of the substance can
be used to describe how long the period of effective substances in the body (Wijayanti et al. 2010).
Plasma pharmacokinetics data flavonoids as the implications for the determination of the frequency of
dispensing on the subject of research. This research is useful as a reference in future research to
application in humans. Further research needs to be done about the pharmacokinetics profile of the
levels of flavonoids from the leaf extract of papaya that is needed in the development of drugs,
particularly the utilization of papaya leaf extract as a medicinal herb.

Whole extract of papaya leaf extract contains compounds still widely bioaktif in addition to flavonoids,
so to process biotransformation in the liver is very slow. Based on the research of Patil et al. (2014)
component in the papaya leaf extract potential as antioxidants include tocopherol, lycopene, quercetin
glycosides, and benzylthiocyanate. Qualitative phytochemical screening to extract papaya leaves contain
flavonoids, alkaloids, glycosides, saponins and tannins (Begum 2014). Flavonoids contained in the
extract of papaya leaves included a flavonol that is routine. Preliminary trials have been done with the
standard routine. Both standard included a flavonol. Flavonoids was detected in the sample of papaya
leaf extract is routine. According to Gregory (2011), the routine is a form of quercetin glycosides
(quercetin glycosides).